Allopurinol Outcome Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Allopurinol Outcome Study (NCT01391325), a non-randomized phase 4 study. The primary outcome is Safety of Allopurinol.

2. Clinical Question

3. Trial Design

The Allopurinol Outcome Study, also called the Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients, is listed as a phase 4 study. It was sponsored by Ardea Biosciences, Inc. The registry describes a non-randomized, unmasked, single-group model, with allopurinol as the intervention. The record lists gout as the condition and enrollment of 1735.

The study description says allopurinol was to be dosed according to the local product label, at the investigator’s discretion, to reach an optimal, medically appropriate dose for each patient. The stated evaluation period was up to six months. The primary safety outcome was assessed every month for 6 months. The study start is listed as 2011-07, primary completion as 2013-01, and status as completed.

Because the study had one treatment group and no randomized control group, its design is descriptive rather than a controlled comparison. Observed events can be reported for people who received allopurinol, but this design alone cannot distinguish events caused by treatment from events due to the underlying condition, other care, or other influences. The registry record does not report a protocol-based comparison group or masking procedures beyond the listed absence of masking.

The record includes secondary outcomes for the proportion with serum urate below 6.0 mg/dL, incidence of gout flares, and mean change from baseline to Month 6 in SF-36 PCS+MCS. Although four outcome measures are listed, the registry record reports no analyses. It does not report a sample-size justification or a detailed statistical analysis plan.

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: 1,735 subjects enrolled in the study; however, only 1,732 were treated. Therefore, 1,732 subjects started the treatment period.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All subjects who received at least one dose of allopurinol

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 subjects who received at least one dose of allopurinol.

6. Primary Endpoint

The registry lists the primary outcome as Safety of Allopurinol, measured over Every month for 6 months..

The primary endpoint is the proportion of subjects who experienced at least one treatment-emergent adverse event during the study. The specified population is all subjects who received at least one dose of allopurinol, and the stated timeframe is every month for 6 months. The endpoint is expressed as a percentage of subjects.

A binary proportion is useful for describing how common an event was in a defined group during a stated observation period. Counting whether a participant experienced at least one event gives a participant-level summary, rather than a count of every event episode. It can therefore answer a practical safety-description question: what fraction of the treated population had at least one event classified as treatment-emergent?

That endpoint does not, by itself, establish that all recorded events were caused by allopurinol. “Treatment-emergent” describes timing in relation to treatment, not proof of causation. Nor does a proportion summarize event severity, duration, recurrence, or the clinical importance of every event. Those aspects require additional definitions and results.

The registry record describes the endpoint and its assessment timeframe but does not report its result. The adverse-event counts listed elsewhere in the posted results are not presented as the primary endpoint estimate, so they should not be substituted for an unreported primary result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant-level percentage describe?

For a binary outcome, each participant is classified according to whether the event occurred during the defined period. The resulting proportion describes the share of the specified population with the event. This is different from a rate based on the number of event episodes: a participant with repeated episodes still meets a “at least one event” definition once. In this study, the primary endpoint is defined as the proportion with at least one treatment-emergent adverse event, among subjects who received at least one allopurinol dose.

To interpret a proportion, its denominator and observation window matter. The primary outcome description identifies a treated population and assessment every month for 6 months. The separate adverse-event results list 1732 subjects at risk. The record does not report a primary-endpoint denominator or result, so the adverse-event group figures should not be presumed to be the primary endpoint calculation.

What would a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimated quantity. It is more informative than a point estimate alone because it indicates which values are compatible with the observed data under a specified method and its assumptions. A narrow interval generally indicates greater precision than a wide interval, though precision does not resolve possible bias or establish causation. The registry record does not report a confidence interval for the primary endpoint.

For a proportion, interval methods need to suit binary data and the amount of information available. General methods can behave differently, particularly when proportions are near a boundary or the number of observed events is small. The posted record does not specify an interval method for this trial, and no primary endpoint estimate is listed for which to assess precision.

Why does the design matter?

Random assignment can help balance measured and unmeasured influences between treatment groups, while a concurrent control group gives a reference for comparative interpretation. This study is listed as non-randomized and single-group, with no masking. Its adverse-event summaries can describe events recorded among people who received allopurinol, but they cannot by themselves provide the counterfactual comparison needed to estimate what would have happened to the same population without that treatment.

Unmasked assessment can also affect event reporting or classification, depending on how outcomes are collected. That is a general methodological concern, not evidence that such bias occurred in this study. The registry record does not report enough information to evaluate the event-collection procedures or any steps taken to limit assessment bias.

How should the listed planning assumptions be read?

The sample-size material is described as a planning illustration computed from an observed effect, not as the trial’s own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it also describes the effect to detect as a stated fraction of the observed effect. For time-to-event tables, the description says values represent the total number of events; for other tables, they represent participants per arm.

Those assumptions do not describe this trial’s single-group, non-randomized design, and an illustrative calculation is not an observed result or observed power. Sample-size calculations are planning tools that depend on assumptions about the effect, variability or event frequency, allocation, and analysis method. They cannot establish that a study had a particular probability of detecting an effect after the fact. The registry record does not report the trial’s own sample-size justification.

What can be inferred from the analysis record?

The registry lists four outcome measures and zero analyses. That means the record does not provide analysis results for those outcomes in the posted results. It does not establish whether analyses were conducted outside the registry record. No statistical model, adjustment strategy, confidence-interval procedure, or hypothesis-testing plan is reported there. General statistical interpretation should therefore remain limited to the endpoint definitions and descriptive adverse-event figures that are actually posted.

For event counts, over-dispersion is a general concern when variation exceeds what a chosen count model expects. It can make model-based uncertainty too small if ignored. However, the primary endpoint is a participant-level binary outcome, and the registry does not report a count-model analysis. The posted record gives no basis for asserting that an over-dispersion adjustment was needed or used.

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("Allopurinol")
n      <- c(1732)
events <- c(954)
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  Allopurinol  1732  954  55.1  52.7  57.4  52.7  57.4  52.7  57.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures: the primary safety outcome and secondary outcomes covering serum urate below 6.0 mg/dL, incidence of gout flares, and mean change from baseline to Month 6 in SF-36 PCS+MCS. When several outcomes are examined, the chance of at least one apparently notable finding can increase if each is tested separately. Statistical methods can address this multiplicity, but the appropriate approach depends on the planned questions and analysis strategy.

The registry record reports zero analyses and does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a detailed testing strategy. It is therefore not possible to determine from the record whether multiplicity was addressed in analyses conducted elsewhere. No results for the listed secondary outcomes are reported in the posted results.

The record also does not report how missing outcome data were handled, the extent of missingness, or whether participants with incomplete follow-up were included in particular analyses. The primary endpoint population is defined as all subjects who received at least one dose, but the record does not provide a primary endpoint result or analysis-population details beyond that definition. The number of subjects at risk in the adverse-event results is listed as 1732, while enrollment is listed as 1735; the record does not explain the difference.

These omissions limit assessment of outcome completeness, potential selection effects, and the robustness of any analysis. They do not demonstrate that data were missing or that an analysis method was unsuitable; those matters are not reported in the registry record.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute myocardial infarction (0.2%), pneumonia (0.2%), acute coronary syndrome (0.1%), atrial fibrillation (0.1%), atrial flutter (0.1%).

The adverse-event results list 1732 subjects at risk in the Allopurinol group. They report 52 subjects affected in the serious adverse-event category and 654 subjects affected in the other adverse-event category. The record does not say whether the same subject could appear in both categories, so the counts should be read separately rather than combined.

The listed serious adverse-event terms are acute myocardial infarction and pneumonia, each reported as 0.2%, and acute coronary syndrome, atrial fibrillation, atrial flutter, and supraventricular tachycardia, each reported as 0.1%. These percentages are the figures attached to the terms in the registry record. The record does not provide additional detail about how the terms were coded, whether a subject could contribute more than one term, or the duration and timing of events.

These summaries describe reported events in the treated group; they do not establish that all events were caused by allopurinol. The study has no comparator arm, and no primary safety analysis result is reported. The counts and term percentages should therefore be interpreted as descriptive safety information, not as comparative estimates or proof of causation.

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

The registry record documents a single-group study in which allopurinol was evaluated in people with gout and hyperuricemia, with safety and serum urate lowering among the stated aims. Its posted adverse-event results provide counts for serious and other adverse-event categories and percentages for selected serious-event terms. Those figures offer descriptive information about events recorded in the Allopurinol group.

The record does not report the primary endpoint result: the proportion of subjects who experienced at least one treatment-emergent adverse event. It also does not report results for the listed secondary outcomes. No primary estimate or confidence interval is available in the registry record to show the magnitude or precision of that endpoint. The adverse-event counts and term percentages cannot be treated as substitutes for an unreported primary result.

The design also sets an important limit on interpretation. A non-randomized, single-group study without masking does not provide a control group for comparison. The posted event summaries therefore cannot establish whether event frequency was higher or lower than it would have been under another treatment or without treatment. Treatment-emergent timing does not, by itself, prove a treatment caused an event.

The record’s enrollment figure and adverse-event at-risk figure are not identical, and the reason is not reported in the registry record. It also does not describe missing-data handling, outcome-analysis methods, or a sample-size justification. These gaps make it difficult to assess precision, completeness, and analytic choices from the registry entry alone.

In short, the posted results support a descriptive account of the adverse-event information recorded for the treated group. They do not provide a reported primary endpoint estimate or a comparative conclusion about allopurinol. Any broader interpretation would require information and analyses not reported in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates why a study’s design and its reported outcome results must be read together. A safety endpoint can be defined clearly as the proportion of treated subjects with at least one treatment-emergent adverse event, yet the registry record does not report that primary result. Describing the endpoint is not the same as reporting its estimate, and adverse-event category counts do not fill that gap.

The study also shows the distinction between safety description and comparative inference. A single-group design can record events during treatment, but without a control group it cannot estimate a treatment contrast. Non-randomized allocation and absence of masking further mean that causal interpretation depends on evidence the posted record does not provide. This is a design limitation, not a reason to disregard the descriptive counts.

For statistical readers, the different population figures deserve attention: the record lists enrollment of 1735 and 1732 subjects at risk for the adverse-event results, but does not explain the difference. Clear reporting of analysis populations and denominators is essential for interpreting a proportion. The record’s lack of an endpoint analysis, confidence interval, and missing-data description also prevents a full assessment of precision and robustness.

Finally, the planning illustrations are not the trial’s own design or evidence of observed power. Their stated two-arm assumptions do not match the registered single-group model. Keeping design assumptions, observed summaries, and planned calculations separate is important for avoiding stronger conclusions than the registry data support.

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 main trial-specific limitation is the absence of a comparator group. The study is listed as non-randomized, single-group, and unmasked, so its event summaries cannot establish a comparative treatment effect or isolate treatment causation. The record does not describe any methods that would supply a control-based comparison.

The primary endpoint is defined, but its result is not reported in the registry record. The listed adverse-event figures do not provide the primary proportion of subjects with at least one treatment-emergent adverse event. The registry also reports zero analyses, and results for the listed secondary outcomes are not reported. Consequently, there is no posted estimate or confidence interval with which to assess the primary endpoint’s magnitude and precision.

Several details needed to evaluate the summaries are not reported in the registry record, including missing-data handling, the analysis population used for each outcome, event-collection and classification procedures, and the statistical analysis methods. Enrollment is listed as 1735, whereas the adverse-event results list 1732 subjects at risk; the reason for this difference is not reported. The serious and other adverse-event categories are presented separately, but overlap between them is not explained.

The record’s sample-size assumptions are described as a planning illustration rather than the trial’s own design. They use a two-arm planning framework, whereas the registered study is a single-group trial. The registry record does not report the original sample-size justification, so the illustration should not be taken as evidence about the trial’s planned or observed statistical power.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Allopurinol Outcome Study — NCT01391325.
• Registry record last updated 2014-06-17; status last verified 2014-05.
• Results first posted 2014-06-17.
• 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

The registry record describes the Allopurinol Outcome Study (LASSO) as a phase 4, non-randomized, unmasked, single-group study in people with gout. Allopurinol was the intervention, with dosing according to the local product label at the investigator’s discretion. Enrollment is listed as 1735; the study status is completed.

The primary endpoint was the proportion of subjects who experienced at least one treatment-emergent adverse event, assessed every month for 6 months among subjects who received at least one dose. The primary endpoint result is not reported in the registry record. The posted adverse-event results list 1732 subjects at risk, 52 affected in the serious category, and 654 affected in the other category, alongside selected serious-event term percentages.

Secondary outcomes include serum urate below 6.0 mg/dL, gout flares, and SF-36 PCS+MCS change. The registry lists four outcome measures and zero analyses. It does not report outcome analysis methods, missing-data handling, or the reason enrollment and at-risk figures differ.