Long-Term Study of Nitisinone to Treat Alkaptonuria: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Long-Term Study of Nitisinone to Treat Alkaptonuria (NCT00107783), a randomized phase 2 study. The primary outcome is Change in Total ROM Worse Hip.

2. Clinical Question

3. Trial Design

This was a phase 2, randomized, single-masked, parallel-group study of nitisinone in alkaptonuria. The registry lists an enrollment of 40. Participants were assigned to control or nitisinone-treated groups, with 20 participants in each group in the posted primary outcome results. The nitisinone-treated group received 2 mg orally once daily. The control arm is described as “No treatment”; the brief summary instead says that this group took only their regular medicines. The registry record does not resolve the difference between these descriptions.

The brief summary describes the study as lasting 3 years and focused on long-term use of nitisinone for joint problems. The primary outcome was measured at baseline and at 36 months. The record lists a start date of 2005-01, primary completion in 2009-04, and status as completed. It does not report the total study duration for each participant or explain how the 36-month endpoint relates to the listed dates.

The summary describes potential eligibility for people aged 30 to 80 years with alkaptonuria, hip involvement, and at least one remaining hip joint. It also says candidates were recruited from participants in another protocol and could take part in both protocols at the same time. These are descriptions of the intended population, not a full account of who ultimately enrolled.

The registry identifies the primary analysis population as intention to treat. It does not report which individuals were masked, the randomization procedure, allocation concealment, or whether participants and clinicians knew group assignments. The rationale for the sample size, the trial’s original power assumptions, and the prespecified statistical analysis plan 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:

Analysis population for the primary outcome, as defined in the registry: Intention to treat.

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 Change in Total ROM Worse Hip, measured over Measured at baseline and at 36 months.

The primary endpoint was change from baseline in total range of motion of the worse hip at 36 months. The measurement combines external and internal hip rotation, in degrees. During assessment, the participant lies supine and flexes the hip and knee to 90 degrees; an examiner uses a goniometer to measure each rotation. The endpoint therefore represents a continuous measurement of hip movement rather than a count of events or a yes-or-no clinical outcome.

Range of motion is used in this study as a measure of joint movement in participants with alkaptonuria and hip involvement. The registry summary links the condition’s accumulation of homogentisic acid with arthritis and limited joint movement, and describes the study as examining long-term treatment in relation to joint problems. The endpoint focuses on the worse hip, which provides a defined joint for comparison across participants. The registry record does not explain how the worse hip was selected if both hips were affected, or how changes in the measurement were expected to relate to participants’ everyday function.

A positive group difference means the mean change was higher in the nitisinone-treated group than in the control group, using the comparison’s stated direction. The posted means were 1.6 degrees for the nitisinone-treated group and -9.1 degrees for control; the reported difference was 10.7 degrees. These summaries describe average change, not the range of individual responses. The registry record does not report a threshold for a clinically important difference, so the size of the observed estimate cannot by itself establish the practical importance of the change.

7. Results Posted in the Registry

• Nitisinone-treated: mean 1.60 versus -9.10 on control; difference 10.70 (95% CI -3.74 to 25.14), standardized effect d = 0.46; z-test p = 0.146.

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.

Change in Schober's Test

• 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:
  • Nitisinone-treated: mean 0.12 versus -0.06 on control; difference 0.18 (95% CI -0.59 to 0.95), standardized effect d = 0.15; z-test p = 0.649.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Nitisinone-treated and the control. The interval gives the range of effects that remain compatible with the data.

Change in Functional Reach Assessment

• 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:
  • Nitisinone-treated: mean -1.86 versus -1.21 on control; difference -0.65 (95% CI -3.04 to 1.74), standardized effect d = -0.18; z-test p = 0.594.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Nitisinone-treated and the control. The interval gives the range of effects that remain compatible with the data.

Change in Timed Get up and go

• 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:
  • Nitisinone-treated: mean -1.33 versus -0.54 on control; difference -0.79 (95% CI -3.21 to 1.63), standardized effect d = -0.21; z-test p = 0.522.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Nitisinone-treated and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover spinal mobility, functional reach, a timed mobility task, and walking distance. The posted comparisons do not form a consistent pattern of clearly separated group means: the estimates include small differences in both directions, and their confidence intervals include zero. Taken together, these results do not provide a more precise or decisive account than the primary endpoint. They are measures of related but distinct aspects of movement and function, so a difference in one would not automatically imply a difference in another.

The secondary outcomes complement the primary measure by broadening the clinical picture beyond hip range of motion. However, the registry record does not report a prespecified hierarchy among these outcomes, or a stated plan for interpreting their results collectively. No secondary analyses are listed as reported analyses in the registry record. The estimates should therefore be treated as exploratory descriptions rather than as independent confirmation of the primary finding.

Each additional outcome creates another opportunity for an apparently notable result to arise from sampling variation. General explanation: when many hypotheses are tested, the chance of at least one false-positive finding can increase unless the analysis accounts for multiplicity or the outcomes are interpreted under a prespecified strategy. The record does not report such a strategy. This does not establish that any secondary result is false; it means that unadjusted secondary p-values or isolated estimates would carry less evidential weight than a primary outcome protected by a clear, prespecified analysis plan.

The secondary groups include 18 control participants and 19 nitisinone-treated participants for each posted outcome. These counts differ from the 20 participants per group in the primary result. The record does not explain the reasons, the pattern of missing observations, or the handling of missing data. That uncertainty further limits comparisons across endpoints and makes it difficult to determine whether the secondary results represent the same randomized population in practice.

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

• Change in Schober's Test
• Change in Functional Reach Assessment
• Change in Timed Get up and go
• Change in 6 Minute Walk Test (6MWT)

9. Statistical Interpretation

10. Statistical Methods Explained

What kind of outcome was analyzed?

The primary measure is continuous: each participant’s change in hip range of motion is expressed in degrees, and the posted group summaries are means and standard deviations. A mean describes the arithmetic average within a group. The standard deviation describes how much participant measurements vary around that average. It is not the uncertainty in the mean itself; that uncertainty depends both on variability and on the number of observations.

The comparison is a difference between two group means. The registry reports the control mean as -9.1 degrees and the nitisinone-treated mean as 1.6 degrees, with a mean difference of 10.7 degrees. The contrast is expressed in the same units as the outcome. Its sign depends on the stated ordering of the groups, so interpretation should retain the comparison’s direction rather than treating a positive or negative value as inherently favorable.

What does the confidence interval describe?

A confidence interval is a range of values compatible with the observed data under the method’s assumptions. In repeated use of the same procedure, intervals constructed at the stated confidence level would cover the true parameter at that rate. A particular interval is not a probability distribution for the true value. Here, the reported interval from -3.738 to 25.14 degrees includes zero, the value corresponding to no difference in mean change. It also includes values on either side of zero, indicating uncertainty about direction as well as magnitude.

The width of an interval depends on the variability of the measurements, the number of observations, and the analysis method. General explanation: more variable outcomes and smaller groups usually yield less precise mean comparisons, all else equal. In this study, the primary analysis includes 20 participants in each group, and the standard deviations are relatively large compared with the estimated difference. These features help explain why the interval spans both negative and positive values. The registry record does not report additional adjustment variables or a model-based analysis that would change this interpretation.

How should the p-value be read?

The unadjusted p-value is 0.146. General explanation: a p-value measures how unusual data at least as discrepant as those observed would be under a null model and the test assumptions. It does not give the probability that the null model is true, the probability that a result occurred by chance, or the magnitude of an effect. It also does not establish that two treatments are equivalent. The interval and the estimate provide information about plausible magnitudes that the p-value alone does not convey.

The record labels the comparison as unadjusted. It does not report whether other analyses were performed but not posted, what significance threshold was specified in advance, or whether multiplicity correction was planned. Thus, the p-value should not be interpreted as a complete account of the trial’s statistical decision process.

Why can variability matter?

General explanation: when an outcome varies more across participants, an average can be estimated less precisely from a fixed number of observations. If the distribution has heavier tails or more outliers than a normal model allows, a simple normal-based analysis can also misstate uncertainty; this phenomenon is often described as over-dispersion relative to the model. The registry provides standard deviations but does not report distributional checks, outlier handling, or a model addressing such concerns. There is therefore no basis in the record to say whether these issues affected the analysis.

The posted primary comparison is a mean-based summary, so it can conceal differences in the shape of the participant-level distributions. For example, similar means may coexist with different patterns of individual response. No individual data, quantiles, or distribution plots are reported in the record. This limits what can be concluded about heterogeneity.

What does intention to treat mean?

The registry states that the primary outcome population was intention to treat. General explanation: an intention-to-treat approach aims to analyze participants according to their randomized assignment, regardless of treatment adherence or later changes, preserving the randomized comparison. The label alone does not establish how missing endpoint measurements were handled, whether every randomized participant was included, or how deviations were treated. Those implementation details are not reported in the registry record.

There were 20 participants in each primary outcome group. The secondary outcomes have 18 participants in control and 19 in the nitisinone-treated group. The record does not explain why the available counts differ across outcomes, whether these represent missing measurements, or how such missingness was addressed. A complete evaluation would need that information alongside the analysis methods.

What is not documented?

The registry record does not report the original sample-size calculation, its target effect, or its assumed variability. It does not report the planned statistical model, covariate adjustment, handling of protocol deviations, interim analyses, or multiplicity strategy. Nor does it list reported analyses for the secondary outcomes. These absences do not prove that the study team did not make such decisions; they mean the decisions cannot be assessed from the registry record.

The planning illustrations based on observed effects are separate from the trial’s original design. They use stated assumptions and estimate how many participants per arm would be needed under those assumptions. They are not evidence about the probability that this completed trial detected an effect. General explanation: power is a design property for a specified effect, variability, and analysis procedure; it is not a retrospective score that tells whether a particular observed result is reliable.

11. Confidence Intervals and Precision

The primary estimate is a mean difference of 10.7 degrees, with a 95% confidence interval from -3.738 to 25.14 degrees. The interval includes zero, so the posted data are compatible with no average difference as well as with differences in either direction. Its endpoints also indicate that a range of magnitudes remains plausible under the analysis. The point estimate alone gives a less complete picture than the estimate and interval together.

Precision is limited in part by the number of observations and the variability in the outcome. The primary result includes 20 participants per group, while the group standard deviations are 24.7 degrees and 21.8 degrees. Standard deviations describe variation among participants; the confidence interval describes uncertainty in the group contrast. These are related but are not interchangeable quantities.

The interval is not a guarantee that the true difference lies within its endpoints, nor does it indicate that all effects inside it are equally likely. It expresses uncertainty under the statistical procedure and its assumptions. The registry record does not report sensitivity analyses, distributional diagnostics, or alternative intervals that would help evaluate the dependence of the result on those assumptions.

The unadjusted p-value of 0.146 is consistent with substantial uncertainty, but it does not replace the interval’s direct account of compatible differences. Since the interval spans zero, the data do not precisely establish a direction. Since it also spans nonzero values, the data do not demonstrate that the groups are equivalent. A formal equivalence conclusion would require a prespecified equivalence margin and an analysis designed for that question; neither is reported in the registry record.

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 planning estimates are participants per arm, not totals across both groups and not event counts. They are illustrations based on the observed effect rather than the trial’s own documented design calculation. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect equal to the stated fraction of the observed effect. The original trial’s sample-size assumptions are not reported in the registry record.

The 80% power column gives the approximate number of participants per arm for a design with an 80% chance of detecting the specified effect under those assumptions, if that effect is the true effect and the analysis assumptions hold. The 90% power column gives the corresponding approximate number per arm for a design with a 90% chance. These are planning probabilities for a hypothetical design, not guarantees about results.

Rows describe planning for 100%, 75%, or 50% of the observed effect. In general, smaller effects are harder to distinguish from random variation and need more participants. Thus the estimates rise as the target effect is reduced from the full observed effect to a smaller fraction. The illustrations do not account for every possible feature of a future study, such as different outcome variability or a changed analysis method.

These figures are not observed power. Observed power is not a useful substitute for interpreting the uncertainty in the completed trial: the estimate and confidence interval describe what the primary data can support. The planning calculations instead show how sample requirements would change under the stated assumptions and effect scenarios.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 10.700; pooled standard deviation σ = 23.295.
2. n = 2 × (1.96 + 0.842)² × 23.295² / 10.700² = 74.4, rounded up to 75 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
delta <- 10.7                      # observed difference in means
sigma <- 23.2951711734428                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(107783)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 75 (80% power), 100 (90% power)
 75% of observed effect: n per arm = 133 (80% power), 178 (90% power)
 50% of observed effect: n per arm = 298 (80% power), 399 (90% power)
power.t.test: 75.4 
Simulated power at n = 75 per arm: 0.797 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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

Multiplicity arises when a study examines several endpoints, time points, subgroups, or statistical contrasts. General explanation: testing multiple questions can increase the chance that at least one result appears statistically unusual even if none reflects a real difference. Common strategies include designating one primary endpoint, specifying a hierarchy, or adjusting inference across a family of tests. The registry identifies a primary endpoint and lists four secondary outcomes, but a formal multiplicity strategy is not reported in the registry record. The record also does not report whether other time points or subgroup analyses were planned.

The p-value attached to the primary comparison is unadjusted, and the secondary comparisons are also listed with unadjusted p-values. Without a documented analysis plan, it is not possible to determine whether the primary test was intended to stand alone, whether secondary findings were exploratory, or how multiple results were to influence interpretation. The number of posted outcomes alone does not establish which analyses were conducted or omitted.

The registry labels the primary population intention to treat. It does not report how missing primary measurements were handled, whether all randomized participants contributed to the analysis, or whether imputation or another method was used. The secondary endpoint counts are 18 in control and 19 in the nitisinone-treated group, compared with 20 per group for the primary endpoint. The reasons for these counts and whether missingness was related to outcome or treatment are not reported in the registry record.

Missing data can affect estimates when participants without measurements differ systematically from those with measurements. General explanation: an analysis limited to participants with observed outcomes may be biased if the likelihood of a missing measurement is related to treatment or the outcome, while imputation methods also depend on assumptions. The record does not give enough information to assess these possibilities. It also does not report protocol deviations, adherence, sensitivity analyses, or a detailed definition of the analysis populations. These limitations restrict evaluation of the robustness of the results, but do not by themselves show that the posted analyses are biased.

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: atrial fibrillation (5.0%), keratitis (5.0%), bile duct stone (5.0%), accidental overdose (5.0%), liver enzyme elevation (5.0%).

The serious adverse event summaries list 0 of 20 participants affected in the control group and 6 of 20 in the nitisinone-treated group. For other adverse events, the figures are 10 of 20 in each group. These are counts of participants affected as recorded, not measures of causal attribution. The registry record does not establish whether the serious events were judged related to treatment, how events were defined, or how long participants were followed for safety.

The serious-event terms listed are atrial fibrillation, keratitis, bile duct stone, accidental overdose, liver enzyme elevation, and muscle injury, each reported as 5.0%. The record does not identify the group attribution for each listed term, and the terms should not be assigned to a particular arm from this information alone. Death counts are not reported in the registry record.

With 20 participants in each group, these counts are descriptive and provide limited precision about uncommon harms. They should be read alongside the incomplete details about attribution, event timing, severity, and follow-up. They do not by themselves establish that an event was caused by a treatment or that an unlisted event did not occur.

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

The registry results describe a randomized comparison of nitisinone and control for people with alkaptonuria, with change in the worse hip’s total range of motion as the primary outcome at 36 months. The posted mean difference is positive, but its confidence interval includes zero and spans a range of possible differences. The result is therefore uncertain in both direction and magnitude. It does not establish a clear between-group difference, and it does not establish that the groups are equivalent.

The point estimate and uncertainty should be considered together. A 10.7-degree difference is the estimated contrast in these posted data; it is not a guarantee of what another group of participants would experience. The confidence interval represents sampling uncertainty under the analysis method, but cannot address every source of uncertainty, such as missing-data assumptions or limitations in the outcome measurement. The registry does not report a threshold for clinical importance, so statistical estimates alone cannot determine whether any particular magnitude would matter to participants.

The secondary outcomes offer additional measurements of function and movement, but they are not a substitute for a well-defined primary comparison. Their unadjusted results and the absence of a reported multiplicity strategy make isolated secondary findings less conclusive. Safety counts are also descriptive; the record does not establish causal relationships between treatment and individual adverse events.

More broadly, the record does not report the detailed statistical plan, original sample-size justification, handling of missing outcomes, or participant-level results. Those omissions limit the ability to independently assess analysis choices and robustness. The findings should be understood as the estimates and event counts posted for this completed study, with uncertainty about how well they generalize beyond its participants and setting. They do not, on their own, establish a treatment recommendation or a definitive conclusion about long-term effects.

17. Why This Trial Matters Statistically

This trial is statistically informative because it puts a continuous joint-movement outcome into a randomized comparison, rather than relying only on uncontrolled change over time. Random assignment is intended to make treatment groups comparable on average, though the registry record does not report the randomization procedure or concealment details. The posted result makes the uncertainty visible: an estimated group difference is accompanied by an interval that includes zero and extends across a broad range.

The study also illustrates why a point estimate and a p-value are not enough. The mean difference is 10.7 degrees and the unadjusted p-value is 0.146, but the interval better conveys that the data do not sharply determine the size or direction of a difference. This is particularly relevant in a study with 20 participants in each group and substantial variation in the primary outcome.

Several outcomes were assessed, and the registry record lists four secondary measures alongside the primary endpoint. This makes multiplicity and prespecification important to interpretation. Without a reported strategy for prioritizing or adjusting analyses, secondary results should not be treated as a series of independent confirmations. Similarly, different participant counts across outcomes raise questions about missing measurements that cannot be resolved from the record.

The planning illustrations also demonstrate a general design principle: studies aimed at detecting smaller effects generally require larger groups, all else equal. They are useful as scenario-based planning information, while the original sample-size justification for this trial is not reported. Overall, the record offers a concrete example of how design, outcome variability, precision, multiplicity, and incomplete reporting shape what can be inferred from a clinical trial.

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.

The primary comparison is based on 20 participants per group, and the confidence interval is broad enough to include differences on either side of zero. This limits precision. The registry record does not report baseline characteristics, so readers cannot assess how similar the groups were on measured clinical features or evaluate the extent of any baseline imbalance.

The secondary outcomes have fewer posted observations: 18 in control and 19 in the nitisinone-treated group. The record does not explain why those counts differ from the primary endpoint counts, or how missing measurements were handled. No individual-level data, distributions, or detailed analysis populations are reported. These omissions prevent assessment of missingness patterns and participant-level variation.

The endpoint is a goniometric measure of the worse hip, but the registry does not report measurement reliability, assessor training, assessor masking, or the rule used to select the worse hip. The study is described as single-masked, but which parties were masked is not reported. These details matter when an outcome includes an examiner’s measurement.

The original sample-size calculation, statistical analysis plan, multiplicity approach, interim analyses, adherence summaries, and sensitivity analyses are not reported in the registry record. The record also does not state whether adverse events were considered treatment-related or give their timing and follow-up duration. Finally, the eligibility description is limited and the trial drew candidates from another protocol. The record does not provide enough information to determine how closely the enrolled group represents people with alkaptonuria outside that setting.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Long-Term Study of Nitisinone to Treat Alkaptonuria — NCT00107783.
• Registry record last updated 2021-08-26; status last verified 2010-12.
• Results first posted 2011-01-19.
• 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

The registry record identifies a completed, randomized, single-masked, parallel-group phase 2 study of nitisinone for alkaptonuria, with enrollment of 40. The nitisinone-treated group received 2 mg orally once daily; the control arm is described as “No treatment,” while the brief summary says control participants continued regular medicines.

The primary outcome was mean change from baseline in total range of motion of the worse hip at 36 months. The posted group means were -9.1 degrees in control and 1.6 degrees with nitisinone; the mean difference was 10.7 degrees, with a 95% confidence interval from -3.738 to 25.14 degrees and an unadjusted p-value of 0.146. Secondary outcomes cover other measures of mobility and function. The record does not report the original sample-size justification, detailed statistical plan, multiplicity strategy, or handling of missing data.