Safety of Urate Elevation in Parkinson's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety of Urate Elevation in Parkinson's Disease (NCT00833690), a randomized phase 2 study. The primary outcome is Tolerability.

2. Clinical Question

This was a phase 2 study with three parallel groups. Its stated purpose focused on safety, tolerability, and urate elevation rather than on demonstrating an effect on the rate of Parkinson disease disability progression. The registry record does not report a primary clinical disability outcome.

3. Trial Design

The registry describes a randomized, double-blind, placebo-controlled, parallel-group phase 2 trial sponsored by The Parkinson Study Group. It enrolled 75 participants with Parkinson disease. The study status is completed; the recorded start was 2009-06 and primary completion was 2012-12. The official title describes a dose-ranging study of oral inosine in early Parkinson disease.

Participants were assigned to placebo, an inosine regimen intended to produce mild urate elevation, or an inosine regimen intended to produce moderate urate elevation. The active-treatment descriptions specify 500 mg of active substance per capsule, 1 to 6 capsules per day in up to 3 divided doses, with dosing titrated toward the assigned serum urate range. The descriptions state a duration of 2 years. The registry record does not provide additional details about treatment adherence, how titration decisions were made, or the precise randomization procedure.

The main reported outcome is tolerability, expressed as the percentage of participants in each group meeting the registry definition. The posted primary result concerns the 6-month assessment. The trial also lists a 24-month assessment in the outcome description, but a corresponding primary result is not reported in the registry record. The outcome definition counts treatment continuation without a prolonged dose reduction due to adverse experiences, with a prolonged reduction defined as >48 consecutive days or >73 cumulative days.

Secondary measures include cerebrospinal fluid (CSF) urate, CSF urate as a proportion of baseline serum urate, and serum urate. The record lists measures for all participants and, for some outcomes, separately for females and males. The posted secondary results include a 12-week CSF assessment and a baseline serum urate assessment. The trial’s original design assumptions, including its planned statistical power and sample-size justification, are not reported in the registry record.

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:

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 Tolerability, measured over 6 months.

The primary endpoint is tolerability at 6 months, reported as the percentage of participants in each group who met the outcome definition. The definition focuses on whether assigned treatment could continue without a prolonged dose reduction due to adverse experiences. It treats a reduction lasting >48 consecutive days or >73 cumulative days as prolonged. The description identifies the cumulative threshold as 10% of the total 2-year follow-up.

This type of endpoint is used to summarize the practical ability to remain on an assigned regimen, rather than to measure disease progression or a biological response alone. It combines the treatment experience and dose-management consequence into a participant-level outcome: whether prolonged reduction was needed under the stated definition. Because the outcome is a proportion, the group percentages convey how often that definition was met in each arm.

The endpoint should not be read as a complete account of all adverse experiences. It is specifically defined around continuation without a prolonged dose reduction because of adverse experiences. Other safety information is reported separately as serious and other adverse-event counts. The registry description says tolerability was assessed after 6 and 24 months on study drug, while the posted primary result addressed is at 6 months. The 24-month primary result and the original statistical analysis plan are not reported in the registry record.

7. Results Posted in the Registry

• [B:]Mild: 95.8% (23/24) versus 96.0% (24/25) on control; risk difference -0.2 percentage points (95% CI -11.3 to 10.9), risk ratio 1.00 (0.89–1.12); unadjusted two-proportion z-test p = 0.976.
• [C.]Moderate: 100.0% (26/26) versus 96.0% (24/25) on control; risk difference 4.0 percentage points (95% CI -3.7 to 11.7), risk ratio 1.04 (0.96–1.13); unadjusted two-proportion z-test p = 0.303.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

CSF Urate (All Patients)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • [B:]Mild: mean 544.00 versus 427.00 on control; difference 117.00 (95% CI -17.97 to 251.97), standardized effect d = 0.70; z-test p = 0.089.
  • [C.]Moderate: mean 594.00 versus 427.00 on control; difference 167.00 (95% CI 28.64 to 305.36), standardized effect d = 0.92; z-test p = 0.018.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between [B:]Mild and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for [C.]Moderate than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

CSF Urate as a Proportion of Baseline Serum Urate (All Patients)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • [B:]Mild: mean 13.10 versus 9.60 on control; difference 3.50 (95% CI 0.39 to 6.61), standardized effect d = 0.88; z-test p = 0.028.
  • [C.]Moderate: mean 13.40 versus 9.60 on control; difference 3.80 (95% CI 0.71 to 6.89), standardized effect d = 0.91; z-test p = 0.016.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for [B:]Mild than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for [C.]Moderate than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Serum Urate

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • [B:]Mild: mean 4.32 versus 4.54 on control; difference -0.22 (95% CI -0.78 to 0.34), standardized effect d = -0.23; z-test p = 0.441.
  • [C.]Moderate: mean 4.62 versus 4.54 on control; difference 0.08 (95% CI -0.35 to 0.51), standardized effect d = 0.10; z-test p = 0.714.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between [B:]Mild and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between [C.]Moderate and the control. The interval gives the range of effects that remain compatible with the data.

The secondary results cover biological measures related to the study’s stated aim of raising urate. The overall pattern is that the posted 12-week CSF urate means are higher in the inosine groups than in placebo, and the CSF urate proportion of baseline serum urate also has higher means in the inosine groups. In contrast, the baseline serum urate results describe values before the treatment assessment and do not show a clear group difference in the unadjusted comparisons. The registry lists additional sex-specific CSF outcomes, but their results are not reported in the registry record.

These biomarker measures answer a different question from the primary tolerability endpoint. Tolerability concerns whether participants could continue assigned treatment without a prolonged dose reduction due to adverse experiences. CSF and serum urate measurements concern biological response. A pattern in a biomarker can help characterize whether the intervention affected its intended biological measure, but it does not demonstrate an effect on disability progression, symptoms, or other clinical outcomes. No clinical progression result is reported in the registry record.

The secondary findings deserve less weight than a prespecified primary result because there are multiple outcomes and comparisons, and the registry does not report a multiplicity-adjustment plan or a hierarchy specifying which secondary results were confirmatory. Their p-values are unadjusted. When many comparisons are examined, some can appear noteworthy by chance even when there is no underlying effect. This is a general statistical concern, not a claim that any particular result in this trial is spurious.

The secondary measurements also have outcome-specific group sizes, and the registry does not explain the differences in availability. The posted results should therefore be treated as exploratory evidence about urate measures, with uncertainty and possible selection from missing measurements kept in view. They complement, but do not replace, the primary tolerability result or provide evidence about the study’s longer-term clinical question.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• CSF Urate (All Patients)
• CSF Urate (Females)
• CSF Urate (Males)
• CSF Urate as a Proportion of Baseline Serum Urate (All Patients)
• CSF Urate as a Proportion of Baseline Serum Urate (Females)
• CSF Urate as a Proportion of Baseline Serum Urate (Males)
• Serum Urate
• Serum Urate

9. Statistical Interpretation

10. Statistical Methods Explained

The trial used a randomized, double-blind, parallel-group design. Randomization is intended to make assigned groups comparable on average, including with respect to factors that are measured and factors that are not measured. Masking can reduce the influence of treatment knowledge on participant behavior, clinical management, and outcome assessment. The registry records these design features but does not report the sequence-generation method, allocation concealment procedures, or operational details of masking. Those details are not reported in the registry record.

What does the primary percentage represent?

The primary outcome is binary at the participant level: a participant either meets the registry’s tolerability definition or does not. Group results are expressed as percentages. A risk difference compares the proportion meeting the definition in one group with the corresponding proportion in the comparator group. Its sign indicates the direction of the contrast according to the comparison’s ordering, while an interval that includes zero is compatible with no difference as well as with differences in either direction. The posted results give unadjusted risk-difference comparisons for each inosine regimen versus placebo. Since the registry outcome is expressed as a percentage, it is important to distinguish the underlying proportion scale used for a risk-difference calculation from a display in percentage points; no conversion is needed to understand that the intervals include zero.

A p-value summarizes how incompatible the observed data are with a specified null hypothesis under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of a difference. The p-values in the posted comparisons are described as unadjusted. They do not account for the set of other outcomes or comparisons unless a separate adjustment is specified. No multiplicity-adjustment procedure or primary hypothesis-testing plan is reported in the registry record.

How should the continuous outcomes be read?

CSF and serum urate are reported as means with standard deviations. A mean summarizes the center of the observed values, while a standard deviation describes their spread within a group. A mean difference compares the group means. For example, the registry reports CSF urate means at 12 weeks and comparisons of the mild and moderate groups with placebo. The confidence interval around a mean difference describes the precision of that contrast under the calculation’s assumptions. If it includes zero, values consistent with no mean difference remain compatible with the data. For CSF urate, the mild-group interval includes zero, while the moderate-group interval is entirely above zero. These are unadjusted re-calculations based on posted summary statistics, not a substitute for an analysis using participant-level data or any sponsor analysis not recorded in the registry.

Standard deviations describe variability among measurements, not the uncertainty of the estimated mean difference by themselves. The precision of a mean comparison also depends on the group sizes. Smaller groups generally produce less precise estimates when variability is otherwise similar. The CSF results use fewer participants than the primary tolerability results, as reflected by the group counts attached to those secondary measures. The registry does not report why those outcome-specific counts differ or whether the missing measurements were related to participant characteristics or outcomes.

Why does the outcome type matter?

Binary outcomes reduce each participant’s experience to whether a specified event or condition occurred. This can make results easy to interpret as group proportions, but information about degree, timing, or duration may not be retained by the binary summary. Continuous outcomes retain numerical variation in a biomarker, but their interpretation depends on the measurement scale, distribution, and clinical relevance. A biomarker difference is not automatically a difference in symptoms, function, or disease progression.

Over-dispersion is a general concern for count outcomes when observed variability exceeds what a simple model assumes. It can make standard errors too small if ignored. The principal posted outcome is binary, and the secondary outcomes are means; the registry record does not specify an over-dispersion model or a count-outcome analysis for these results. More generally, the statistical model should match the outcome and its distribution, but the registry record does not report enough detail to establish the full analysis methods.

What can be inferred from the available comparisons?

The comparisons are unadjusted, and the registry reports no sponsor-reported analyses for the posted secondary measures. The primary result also has no reported analysis description beyond the endpoint and posted group comparisons. The comparisons therefore support descriptive and exploratory reading, with uncertainty considered through the intervals, but they do not reveal whether the investigators used additional covariate adjustment, a particular analysis population, or a prespecified hierarchy of outcomes. Those matters are not reported in the registry record.

The registry gives outcome-specific group sizes. Such counts can differ across outcomes because the measured population may differ by assessment or data availability; the reason for the differences in this trial is not reported in the registry record. Without participant-level data, it is not possible to assess missing-data patterns, verify outcome derivations, or examine whether the analysis handled repeated measurements as planned. The primary assessment is described at 6 months, but the registry does not report whether the analysis included all randomized participants, only participants with observed outcomes, or another population definition.

The sample-size illustrations are separate from the trial’s original design. They use observed effects and stated planning assumptions to show how a future two-arm study’s size might vary with the target effect and power. They do not provide evidence that the present trial was adequately powered or that a result without statistical significance reflects absence of an effect. The trial’s own sample-size assumptions and any interim analyses are not reported in the registry record.

11. Confidence Intervals and Precision

Confidence intervals express uncertainty around an estimated contrast. A narrower interval indicates greater precision under the method used; a wider interval leaves a broader range of values compatible with the data. An interval that crosses zero for a difference includes no difference as one possibility. That does not establish that the true difference is zero, and an interval that excludes zero does not by itself establish clinical importance.

For the primary tolerability comparisons, both posted intervals include zero. The mild-inosine comparison is particularly imprecise relative to the near-identical posted group percentages: its interval permits a difference in either direction. The moderate-inosine interval also includes zero, despite the 100.0 group percentage compared with 96.0 for placebo. The p-values, 0.976 and 0.303, are consistent with the absence of clear evidence of a difference in these unadjusted comparisons. The intervals should be considered alongside the limited group sizes rather than interpreted as proof of equal tolerability.

For the 12-week CSF urate mean difference, the interval for mild inosine includes zero, while the interval for moderate inosine lies above zero. For the CSF urate proportion outcome, both intervals lie above zero. These intervals describe the precision of the individual unadjusted comparisons; they do not account for the number of secondary outcomes or comparisons. The baseline serum urate intervals include zero. The registry record does not report a prespecified interval-based decision rule or a clinically meaningful threshold for any of these biomarkers.

Precision is also affected by the number of observations and the variability of the measurements. The secondary CSF group counts are smaller than the counts for the main tolerability results, and the CSF standard deviations indicate variation within groups. The registry record does not provide participant-level data or information about missing measurements, so it is not possible to assess how those features influenced the estimates. Overall, the intervals are a reminder that estimates from this trial are uncertain, and the secondary results warrant cautious interpretation.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the trial’s original design assumptions. The assumptions listed for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The tables report participants per arm for 80% power and participants per arm for 90% power. The time-to-event format, if present, would report total events, but the listed comparisons are not time-to-event outcomes.

The 80% power column describes a planning target in which a future study would have an 80% chance of detecting the specified effect under the stated assumptions, if that effect were the true effect and the analysis assumptions held. The 90% power column uses a higher chance of detecting that same specified effect, which generally requires more participants. These are design calculations, not a retrospective measure of what the completed trial achieved.

Each row changes the assumed target effect relative to the observed effect. Planning for 75% of the observed effect requires more participants per arm than planning for the full observed effect, and planning for 50% requires more still. Smaller effects are harder to distinguish from random variation, so more participants are needed to retain the same target power. Some illustrations can be extremely large when the observed effect is small or uncertain; that reflects the arithmetic of the planning assumptions, not a recommendation about an appropriate future trial size.

These figures are not observed power. They are conditional planning illustrations, and the registry record does not report the original sample-size justification, the effect size targeted by the investigators, or whether their planned calculations used the same assumptions.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.960; treatment proportion p₁ = 0.958; average p̄ = 0.959.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.2799 = 0.5486.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.2799 = 0.2355.
4. n = (0.5486 + 0.2355)² / (-0.0017)² = 221,333.3, rounded up to 221,334 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.96                          # control proportion
p1 <- 0.958333333333333                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(833690)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 221,334 (80% power), 296,302 (90% power)
 75% of observed effect: n per arm = 391,560 (80% power), 524,187 (90% power)
 50% of observed effect: n per arm = 876,684 (80% power), 1,173,630 (90% power)
power.prop.test: 221333.3 
Simulated power at n = 221,334 per arm: 0.801 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists 39 outcome measures and 36 posted secondary results. The record does not report a statistical plan explaining how many outcomes were designated primary or secondary for testing, whether a hierarchy was used, or whether p-values were adjusted for multiple comparisons. The primary endpoint is identified as tolerability, but the registry does not report a broader multiplicity strategy.

Multiplicity matters because each additional outcome or comparison creates another opportunity for a result to appear unusual by chance. A collection of unadjusted p-values should not be interpreted as if every result came from a single isolated test. This is especially relevant to the secondary biomarker results. The unadjusted p-values can describe the individual comparisons under their calculation assumptions, but the registry record does not support treating them as confirmatory findings across the full outcome set.

Missing-data handling is also not reported in the registry record. The number of participants contributing to the 12-week CSF outcomes is lower than the group counts reported for the primary tolerability endpoint, and baseline serum urate has its own group counts. The record does not state why measurements are unavailable, whether missingness differed by treatment group, how missing values were handled, or whether any sensitivity analyses were conducted. Without those details, the direction or impact of missing-data bias cannot be assessed.

The analysis populations are not defined in the posted results. The registry record does not report whether the primary analysis followed an intention-to-treat principle, used a per-protocol population, or applied another population definition. It also does not describe how participants who stopped or reduced treatment were handled in each analysis. Interim analyses, stopping rules, and the original statistical analysis plan are not reported in the registry record. These omissions limit the ability to assess whether the posted comparisons follow prespecified methods and how robust they are to alternative analysis choices.

15. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: arthritis (12.0%), cervical vertebral fracture (4.2%), human ehrlichiosis (4.2%), acute coronary syndrome (4.0%), cerebrovascular accident (4.0%).

The registry reports serious adverse-event counts for each group: 9 for placebo, 2 for mild inosine, and 4 for moderate inosine. The corresponding group sizes at risk are 25, 24, and 26. It also reports counts for other, non-serious adverse events: 18, 22, and 20, respectively. These are counts, not comparisons adjusted for exposure time or differences in follow-up.

The serious-event terms listed in the record include Arthritis at 12.0%, Cervical vertebral fracture at 4.2%, Human ehrlichiosis at 4.2%, Acute coronary syndrome at 4.0%, Cerebrovascular accident at 4.0%, and Depression at 4.0%. The registry excerpt does not identify the treatment group for each listed term or provide enough detail to interpret the percentages as comparative risks. It does not report deaths in the adverse-event group data; death information is therefore not reported in the registry record.

These summaries should be read as descriptive safety reporting. Counts alone do not establish whether an event was caused by treatment, and this record does not provide adjusted or inferential comparisons of adverse-event rates. Serious adverse events and the primary tolerability definition are distinct summaries: the latter is based on prolonged dose reduction due to adverse experiences, not simply on whether a serious event was reported.

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

The posted primary results show high tolerability percentages in all three groups at 6 months under the registry’s specific definition. The unadjusted comparisons do not provide clear evidence of a difference between either inosine regimen and placebo, and their confidence intervals include no difference. The trial does not establish that the groups are equivalent, because no equivalence margin or non-inferiority analysis is reported. Nor do the primary results determine the full safety profile over the stated 2-year treatment period.

The secondary biomarker results show a pattern of higher mean CSF urate and higher CSF urate as a proportion of baseline serum urate in the inosine groups at 12 weeks. These measurements address biological response, not clinical benefit. The registry’s stated motivation was to determine whether a larger study of inosine’s ability to modify disability progression would be appropriate. The posted results do not report whether inosine changes the rate of disability progression, and they should not be interpreted as evidence that it does or does not.

Unadjusted secondary results carry uncertainty because there are multiple listed outcomes and comparisons, and no adjustment strategy is reported in the registry record. Outcome-specific group sizes also differ, while the reasons for unavailable measurements and the missing-data methods are not reported. These factors make the secondary results appropriately exploratory rather than definitive.

The record describes a completed randomized study, but the posted primary result is for 6 months even though the endpoint description also names an assessment at 24 months. The 24-month primary result is not reported in the registry record. The registry also does not report the original sample-size justification, the full statistical analysis plan, or the analysis population. Those gaps limit conclusions about the intended precision and the robustness of the posted analyses.

17. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition matters as much as the label attached to it. Tolerability is operationalized as the ability to continue treatment without a prolonged dose reduction due to adverse experiences. That is a specific, interpretable outcome, but it is not synonymous with absence of adverse events or with long-term clinical benefit. The separate adverse-event summaries answer related but distinct safety questions.

It also shows how a small phase 2 study can generate different kinds of evidence at once. The randomized groups support comparisons of tolerability, while the urate measurements address biological response. Those purposes should not be conflated. A biomarker pattern can inform whether an intervention affects a biological measure, but it does not establish a patient-centered outcome unless that relationship is tested and reported.

The confidence intervals are central to the interpretation. The primary comparisons are not statistically distinguishable from no difference, but that does not prove the treatment groups are equivalent. The range of values compatible with the data matters, particularly when the group sizes are limited. The registry does not report an equivalence or non-inferiority design that would support a formal conclusion of similarity.

Finally, the registry’s secondary outcomes and unadjusted comparisons make multiplicity and transparent reporting important. Missing-data methods, analysis populations, the original sample-size justification, and a multiplicity plan are not reported in the registry record. That information would help readers distinguish confirmatory conclusions from exploratory signals and assess how firmly the results support decisions about a larger study.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Several limitations are specific to the posted record. The primary result is reported at 6 months, while the outcome description says tolerability was assessed at both 6 and 24 months. A 24-month primary result is not reported in the registry record, so the posted comparison cannot describe tolerability across the full stated treatment duration.

The primary outcome is a defined treatment-continuation measure, not a comprehensive measure of adverse experiences. The registry separately lists serious and other adverse-event counts, but does not provide adjusted comparisons, exposure-adjusted rates, group attribution for each top listed event term, or death counts. These summaries therefore do not support detailed comparative safety conclusions.

Outcome-specific group sizes vary, particularly for the CSF measures, and the registry does not explain the reason. Missing-data methods, analysis populations, and sensitivity analyses are not reported. The posted summaries cannot establish whether unavailable measurements were balanced across groups or whether missingness affected the estimates.

The registry lists many outcomes and secondary comparisons, but does not report a multiplicity strategy or identify a confirmatory hierarchy among the secondary results. The p-values are unadjusted, which limits the strength of conclusions drawn from individual secondary findings. The original sample-size justification, assumptions for the trial’s design, interim analyses, and full statistical analysis plan are also not reported in the registry record.

Finally, the posted results focus on tolerability and urate measures. A clinical disability-progression outcome is not reported, despite that being the stated rationale for considering a larger study. The results therefore cannot answer the longer-term clinical question described in the trial summary.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Safety of Urate Elevation in Parkinson's Disease — NCT00833690.
• Registry record last updated 2014-06-05; status last verified 2014-05.
• Results first posted 2014-06-05.
• 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.

22. Record Summary

NCT00833690 is a completed phase 2 randomized, double-blind, placebo-controlled, parallel-group trial sponsored by The Parkinson Study Group. It enrolled 75 participants with Parkinson disease and compared placebo with two oral inosine regimens intended to produce mild or moderate urate elevation.

The posted primary outcome is tolerability at 6 months, defined by the ability to continue assigned treatment without a prolonged dose reduction due to adverse experiences. The reported percentages were 96.0 for placebo, 96.0 for mild inosine, and 100.0 for moderate inosine. Unadjusted comparisons do not establish a difference from placebo, and the confidence intervals include no difference.

Secondary results include CSF and serum urate measures. The CSF outcomes at 12 weeks show higher posted means in the inosine groups than in placebo, but these are unadjusted secondary findings. The registry does not report the 24-month primary result, the original statistical plan, multiplicity adjustment, missing-data methods, analysis populations, or a clinical disability-progression result.