Hydroxychloroquine in Untreated B-CLL Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Hydroxychloroquine in Untreated B-CLL Patients (NCT00771056), a na phase 2 study. The primary outcome is Percentage of Participants With Response.

2. Clinical Question

This is a question about the proportion of participants meeting a response definition during treatment, not a direct comparison of hydroxychloroquine with another treatment or with no treatment. Without a concurrent comparator, the registry record cannot establish how the observed course would differ under another treatment strategy. The outcome description identifies a reduction in ALC, but does not specify a threshold, measurement schedule for the endpoint, or rules for handling participants whose response status is unknown.

Time to Next Treatment is listed as a secondary outcome. Its result and analysis are not reported in the registry record. The study is marked terminated, but the registry record does not give a reason for termination. These details limit what can be concluded about the planned clinical question and its results.

3. Trial Design

The registry identifies this study as phase II, with a single-group model and no masking. Allocation is recorded as NA. Enrollment is listed as 23. The study status is terminated. The start date is recorded as 2008-07, and primary completion is recorded as 2012-01. These registry entries describe the trial record; they do not explain why the study was terminated or whether the recorded enrollment corresponds to the number assessed for the primary outcome.

The intervention was hydroxychloroquine, described as 400 mg by mouth daily for up to one year. The registry summary says participants would be monitored for disease status and adverse reactions after two weeks and then every 4 weeks. Ophthalmologic exams were required at baseline and every 6 months, or sooner if visual disturbances developed. These are descriptions of the planned regimen and monitoring in the registry summary, not evidence that every participant followed the same schedule or completed treatment.

The stated primary outcome was the percentage of participants with a reduction in ALC, with a timeframe of 1 yr. The secondary outcome listed was Time to Next Treatment. The record lists two outcome measures, but does not provide a primary endpoint result, a secondary outcome result, or an analysis. It also does not report an analysis population, the extent of missing outcome data, or the statistical methods used by the investigators.

Because the design has no concurrent control group, it can describe outcomes among participants receiving the study regimen but cannot make a randomized between-group estimate of treatment effect. Changes over time in a single group may reflect influences other than the intervention. The registry record does not report a protocol rationale, sample-size justification, or reason for selecting the design.

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

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 Percentage of Participants With Response, measured over 1 yr.

The primary endpoint is titled “Percentage of Participants With Response.” Its description defines response as a reduction of the absolute lymphocytic count (ALC), and its timeframe is 1 yr. This is a binary outcome at the participant level: a participant either meets the response definition or does not, according to the study’s criteria. The reported endpoint would then express the proportion meeting that definition.

A response proportion can be useful in an early-phase, single-group study because it describes how often a specified outcome occurred among participants receiving the regimen. A clear response definition is essential to interpreting that proportion. The registry record does not state the required amount of ALC reduction, how the count was measured for response assessment, or how participants with unavailable measurements were classified. Consequently, the endpoint title and description alone do not fully establish how response status was assigned.

The registry record does not report the observed response percentage, a confidence interval, or an analysis. It therefore does not permit assessment of the endpoint’s estimated magnitude or precision. Even if a response proportion were reported, a single-group endpoint would describe observed outcomes in that group; it would not by itself show what would have happened under a comparator condition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of endpoint is this?

The primary endpoint is a percentage of participants with a response, where the response description is a reduction in ALC. Statistically, this is a binary outcome for each participant: the response criterion is either met or not met. A proportion summarizes the share of assessed participants who meet the criterion. The registry record does not state the criterion’s required magnitude, so the operational definition cannot be fully reconstructed from the outcome description.

What can a single-group estimate show?

In general, a single-group proportion describes outcomes observed among participants in that group. It does not estimate a contrast between treatment strategies. A controlled comparison can help distinguish outcomes associated with one strategy from outcomes under another; this study’s registry design does not include such a concurrent comparator. Even a precisely estimated proportion would therefore remain a description of outcomes in this study group, rather than a randomized estimate of the treatment’s effect relative to another option.

Confidence intervals are a general way to communicate the uncertainty around an estimated proportion. They represent a range of values compatible with the observed data under the chosen statistical method and its assumptions. The registry record does not report a confidence interval or the response estimate, so neither the range nor the precision of the primary result can be assessed. A confidence interval would also not address the design’s lack of a concurrent comparator or uncertainty caused by an unclear endpoint definition.

What analysis details are available?

The registry record lists no analyses. It does not report an analysis method for the primary endpoint, an analysis population, the number assessed for response, or how missing observations were handled. In general, a proportion depends on the definition of both the numerator—participants meeting the response criterion—and the denominator—participants included in the analysis. If participants are excluded because outcome status is unavailable, the resulting proportion may differ from one based on all enrolled participants. Without the analysis details, the registry record does not establish how these choices were made.

For binary outcomes, statistical methods often rely on assumptions about how observations vary across participants. Over-dispersion is a general concern when the observed variability is greater than a model assumes; ignoring it can make uncertainty appear smaller than it is. The registry record does not say that over-dispersion was assessed or identify a model, so it would be inappropriate to infer that such an adjustment was used or required in the sponsor’s analysis.

How should planning illustrations be read?

Any sample-size illustrations associated with the reported statistics are planning exercises, not observed power. The stated assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The registry design itself is single-group, not an equal-allocation comparison between two arms. Those assumptions therefore do not describe the registered design and should not be read as its protocol or as evidence that the study had a particular probability of detecting an effect.

Planning calculations based on an observed effect are also conditional on that effect estimate. The primary response estimate is not reported in the registry record, so the underlying observed effect cannot be evaluated from this record. No sample-size justification or prospective statistical design calculation is reported. The record does not establish that any planning illustration was used to set enrollment or to guide trial conduct.

What does the timeframe tell the reader?

The primary endpoint timeframe is 1 yr, and the regimen is described as continuing for up to one year. A timeframe identifies the period attached to the outcome, but does not by itself specify the assessment visit, the allowable window, or what happens if a participant stops treatment before that time. The registry record does not report these endpoint-assessment rules. Its monitoring description—after two weeks and then every 4 weeks—concerns disease status and adverse reactions in the brief summary; the record does not explicitly state that those visits determined the primary endpoint.

Time to Next Treatment is listed as a secondary outcome. Time-to-event outcomes generally require a definition of the event, a time origin, and rules for censoring participants whose event is not observed during follow-up. Those details and the result are not reported in the registry record. It is therefore not possible to interpret a time-to-event estimate or its uncertainty from the information available.

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("Hydroxychloroquine")
n      <- c(23)
events <- c(13)
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  Hydroxychloroquine  23  13  56.5  34.5  76.8  36.8  74.4  36.6  74.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and Time to Next Treatment as a secondary outcome, and states that there are two outcome measures. The registry record does not report an analysis for either outcome. It also does not report a statistical plan describing how multiple outcomes or analyses were to be handled. When several outcomes are examined, multiplicity is a general statistical issue: repeated testing can increase the chance of a nominally notable result arising by chance. Whether and how that issue was addressed in this study is not reported in the registry record.

Missing data are also important for interpreting a percentage of participants with response. A participant without an endpoint measurement may have an unknown response status; the analysis could exclude that participant, classify the status under a prespecified rule, or use another approach. These choices can affect both the estimated proportion and its uncertainty. The registry record does not report missingness, reasons for missing outcome measurements, or the method used to handle them.

The record does not define the analysis population for the primary endpoint. It is therefore unclear from the registry information whether the response calculation was intended to include all enrolled participants, only those who began treatment, or a different group. No analysis population or missing-data approach should be inferred from the enrollment figure alone. The absence of reported analysis details limits reproducibility and makes it difficult to judge whether the endpoint result, if available elsewhere, corresponds to the planned question.

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.

The registry lists a hydroxychloroquine group with 23 participants at risk for serious adverse events and 0 affected. For other adverse events, it lists 23 at risk and 0 affected. These are the recorded counts in the registry entry; they should be read as counts, not as proof that no adverse event occurred during the study. The registry does not list serious adverse-event terms, and the top serious terms field is empty.

The registry record does not describe the length or completeness of safety follow-up, or explain how events were collected and classified. It does not report a breakdown by event type or severity for other adverse events. Deaths are recorded as null, which means a death count is not reported in the registry record; null should not be interpreted as a reported count of 0.

These limitations matter because safety summaries depend on consistent event definitions and observation. The posted counts alone do not show whether all participants were monitored for the same duration, whether all events were captured, or whether participants discontinued treatment. They also do not support comparison with another regimen, since no concurrent comparator is described.

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

The registry entry establishes that a phase II, single-group study was registered to evaluate hydroxychloroquine in previously untreated B-CLL. The treatment description specifies 400 mg by mouth daily for up to one year. The primary question concerned the percentage of participants with a reduction in ALC at 1 yr, and Time to Next Treatment was listed as a secondary outcome. The registry record also gives adverse-event counts for the hydroxychloroquine group.

It does not report the primary response percentage, a confidence interval, or an analysis. It likewise does not report the secondary outcome result. The available record therefore cannot establish the size or precision of the observed response, nor how many participants had an outcome measurement available at the endpoint timeframe. The adverse-event counts are limited to the posted figures and lack detail on event terms and follow-up completeness. Deaths are not reported as a count.

The design is single-group and has no concurrent comparator. Accordingly, even a reported response proportion would describe outcomes observed among participants in the study group rather than isolate the effect of hydroxychloroquine from other explanations for changes in ALC. The record does not support a randomized comparison, a causal conclusion, or a comparison of relative safety.

The terminated status is a registry designation, but the reason for termination is not reported. It should not be taken as evidence of a particular outcome or trial problem. In practical statistical terms, the record documents the intended clinical question and some design and safety information, while leaving the primary numerical result and key analysis details unavailable.

14. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clearly stated clinical question and the information needed to estimate its answer. The registry describes a response endpoint based on ALC reduction and gives a 1 yr timeframe, but does not report the response proportion or the analysis. Without those items, readers cannot assess the magnitude of the observed outcome or its precision.

The single-group design also illustrates the distinction between describing an outcome and estimating a treatment contrast. A proportion from a treated group can characterize that group, but without a concurrent comparator it cannot show how outcomes differed from another strategy. This distinction remains important regardless of the size of a single-group response estimate.

The record further highlights why endpoint definitions and analysis populations matter. ALC reduction is named as the response criterion, but the threshold and assessment rules are not reported. The registry also does not explain how missing endpoint status was handled. Those details determine what counts as a response and who contributes to the estimate, so their absence makes a result harder to interpret and reproduce.

Finally, planning calculations must be separated from the design actually registered. The assumptions described for planning use equal allocation between two arms, while the registered study is single-group. Such illustrations are not observed power and do not establish the trial’s prospective rationale. These features make the record useful for understanding the intended question and its reporting limitations, while placing clear boundaries on statistical conclusions.

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 details needed to interpret the primary outcome are not reported in the registry record. The response is described as a reduction in ALC, but no threshold or detailed response-assessment rule is given. The record does not say how endpoint measurements were scheduled or what happened when a participant did not have an evaluable measurement at 1 yr. The analysis population and missing-data approach are also not reported.

The registry gives no primary response estimate, confidence interval, or analysis, and it provides no result for Time to Next Treatment. It does not report the analysis method or a statistical plan for handling multiple outcomes. Consequently, the endpoint’s magnitude, precision, and analysis choices cannot be evaluated from the registry information.

The single-group design has no concurrent comparator, limiting interpretation to outcomes within the study group rather than a randomized comparison. The record does not report a sample-size justification or explain why the design was selected. Although planning assumptions are described, they do not match the registered single-group design and are not evidence of the trial’s own design rationale.

The study is marked terminated, but the reason is not reported. The record does not establish whether planned follow-up was completed. Safety reporting is also limited: event terms and follow-up completeness are not given, and deaths are not reported as a count. These are limitations of the registry information and should not be replaced by assumptions about what occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Hydroxychloroquine in Untreated B-CLL Patients — NCT00771056.
• Registry record last updated 2016-08-22; status last verified 2016-08.
• Results first posted 2016-07-26.
• 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.

19. Record Summary

NCT00771056 is a phase II, single-group study of hydroxychloroquine in previously untreated B-CLL. The registry lists enrollment of 23, status as terminated, a start date of 2008-07, and primary completion of 2012-01. The regimen is described as hydroxychloroquine 400 mg by mouth daily for up to one year, with disease-status and adverse-reaction monitoring.

The primary outcome is the percentage of participants with a reduction in ALC at 1 yr; Time to Next Treatment is listed as a secondary outcome. Neither outcome result nor an analysis is reported in the registry record. For the hydroxychloroquine group, the record lists 0 serious adverse events among 23 at risk and 0 other adverse events among 23 at risk. Deaths are not reported as a count. No concurrent comparator is described, and the reason for termination is not reported.