A Natural History Study In Chinese Male Patients With Duchenne Muscular Dystrophy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Natural History Study In Chinese Male Patients With Duchenne Muscular Dystrophy (NCT03760029), a na na study. The primary outcome is Age of Participants When They Failed to Walk.

2. Clinical Question

This question concerns the timing of a clinical milestone in the cohort, rather than whether a therapy changes that timing. The record says the primary analysis used Kaplan-Meier methods and identifies a median age with a 95% confidence interval as the planned summary. However, the numerical median and confidence interval are not reported in the registry record. The record also states that no participant in the ambulatory group aged <6 years had a failure-to-walk event during the study period. That observation is relevant to the analysis, but it does not supply a median for that group.

3. Trial Design

This was a multicenter, prospective, single-cohort natural history study in Chinese male patients with Duchenne muscular dystrophy. The study status is completed. The registry record gives a start date of 2019-07-24 and a primary completion date of 2023-03-21. Enrollment is recorded as 312, while the study description refers to approximately 330 planned participants.

The planned cohort structure distinguished ambulatory participants aged <6 years, ambulatory participants aged >=6 years, and non-ambulatory participants. The approximate target numbers in the study description were 100, 180, and 50, respectively. Participants were expected to visit study sites every 6 months and be observed for at least 24 months. Those who completed the Month 24 visit sufficiently before study completion could be asked to complete a Month 30 visit; the record says some participants would have data collected after Month 24. The arm description states that all participants would be observed for 24-30 months.

There was no random allocation, masking, or parallel control group described. The listed intervention is visit frequency, categorized as other; this describes study follow-up, not an assigned treatment. The design therefore supports descriptions of outcomes over time in the enrolled cohort, but does not establish a like-for-like treatment comparison.

The registry lists 113 outcome measures and zero analyses. It names outcomes involving mutation characteristics, changes in Pediatric Outcomes Data Collection Instrument scores, and responses to EQ-5D-3L dimensions, in addition to the primary milestone outcome. Details beyond the listed descriptions, including the full protocol and any additional analysis procedures, are not reported in the registry record. The study's sample-size justification is 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.

Before assignment: A total of 318 participants were screened of which 6 were screen failures and 312 participants were enrolled at 6 sites in China.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set included all participants who had been enrolled in the study. Here, 'Number of Participants Analyzed' signifies participants included in the Kaplan-Meier analysis. No participant in "Ambulatory participants aged \< 6 years" had an event of "failure to walk".

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: Full Analysis Set included all participants who had been enrolled in the study.

6. Primary Endpoint

The registry lists the primary outcome as Age of Participants When They Failed to Walk, measured over Up to Month 30.

The primary endpoint is the participant's age when they failed to walk, measured in years. The registry describes this as a life-altering clinical milestone. Age was calculated using the participant's birthdate and the date of failure to walk as reported by a caregiver during the study. The primary timeframe was up to Month 30.

This endpoint is a time-to-event measure: the event is failure to walk, and the event time is the participant's age at that milestone. A participant who had not been reported to have failed to walk by the caregiver was censored on the date of their last visit. Censoring allows participants with no observed event during follow-up to contribute information about the period in which they were observed, without treating them as though the event had occurred.

A median age is used to summarize the event-time distribution: it represents the point in the estimated distribution by which half of the relevant event-time experience has occurred, when the data permit that estimate. A 95% confidence interval conveys uncertainty around the estimated median. These summaries can be useful for describing when a milestone occurs in a cohort, while accounting for differing follow-up and censored observations.

The record states that no participant in the ambulatory group aged <6 years had an event. It does not report the numerical median age or its confidence interval for the primary endpoint. The endpoint definition and planned summary are therefore available, but the primary numerical result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a time-to-event endpoint. In general, time-to-event methods are used when the outcome is the time until a defined event, and participants may have different lengths of observation. In this study, the event was failure to walk, and the relevant time was the participant's age when the milestone was reported. The registry says the date of failure to walk was reported by the caregiver and that age was determined from that date and the participant's birthdate.

What Kaplan-Meier analysis does

In general, the Kaplan-Meier method estimates the probability of remaining free of the event over time while accounting for participants whose observation ends before the event is observed. Such participants are censored rather than counted as having experienced the event. The registry specifies that participants without a caregiver-reported failure-to-walk event were censored on the day of their last visit. Censoring retains their observed follow-up information up to that point.

For this endpoint, time is expressed as age rather than simply time since enrollment. That distinction matters when interpreting the result: the target summary is age at the milestone, while the study visits determine when event information and follow-up status were recorded. The registry gives a follow-up period of up to Month 30, with visits planned every 6 months and observation for at least 24 months. More detailed information about the timing of individual observations is not reported in the registry record.

How to interpret a median and confidence interval

In general, the median event time is the point at which the estimated event-time distribution reaches the halfway mark. It is a summary of the distribution, not an age that every participant experiences. A 95% confidence interval expresses uncertainty in the estimated median under the analysis method; it is not a range containing 95% of individual participants' event ages. The registry identifies the median and 95% confidence interval as the primary endpoint summary, but does not report their numerical values.

Estimation can be limited when few or no events are observed. The registry specifically states that no participant in the ambulatory group aged <6 years had a failure-to-walk event. In general, a group with no observed events cannot yield an observed event age from those data, and the estimated event-time curve may not reach the point needed to define a median. The record does not state the resulting group-specific estimate or explain any additional handling of that group.

What censoring assumes

In general, Kaplan-Meier estimation relies on censoring not being systematically related to a participant's future event risk in a way that would distort the estimate, after accounting for the analysis approach. The registry tells readers when participants were censored, but does not report an assessment of this assumption, reasons for missed follow-up, or methods addressing potentially informative censoring. Those details are not reported in the registry record.

What the registry does and does not specify

The listed primary analysis method is Kaplan-Meier. The record also defines the Full Analysis Set as all enrolled participants and says that the number analyzed refers to those included in the Kaplan-Meier analysis. It does not provide the analysis count, event count by group, numerical estimate, confidence interval, or analysis output. The record lists 113 outcome measures but zero analyses. A statistical plan addressing model choices, subgroup procedures, or sensitivity analyses is not reported in the registry record.

General statistical interpretation should distinguish the analysis method from its result. Naming Kaplan-Meier does not reveal the estimated median or its precision; those require the numerical output. Nor does a descriptive time-to-event estimate establish the effect of an intervention. This study is described as a single-cohort natural history study, with no randomized treatment comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 113 outcome measures, including the primary milestone outcome and secondary outcomes involving mutation characteristics, PODCI scores, and EQ-5D-3L responses. It reports zero analyses. A multiplicity strategy—such as a hierarchy of tests, an adjustment procedure, or a designation of which secondary outcomes are confirmatory—is not reported in the registry record. Without that information and the numerical results, the statistical interpretation of multiple outcomes cannot be assessed further.

The primary endpoint description identifies the Full Analysis Set as all participants enrolled in the study. It also explains that the number analyzed is the number included in the Kaplan-Meier analysis. The actual number included in that analysis is not reported in the registry record. The record states that participants without a reported failure-to-walk event were censored at their last visit, but does not give the extent of missing observations, reasons for missingness, or methods for handling missing data beyond this censoring definition.

In general, censoring and missing data are not interchangeable. Censoring means that event-free follow-up is known up to a stated time, while missing data may refer to information that was not obtained. The record gives the censoring rule for participants without a reported event, but does not describe the completeness of caregiver reports or the follow-up process for participants who discontinued visits.

Any additional analysis populations, rules for excluding participants, sensitivity analyses, or methods for addressing missing outcome information are not reported in the registry record. The listed Full Analysis Set definition should therefore not be taken as evidence that every enrolled participant contributed to every outcome measure.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events separately for three participant groups. It records zero participants with a serious adverse event in the ambulatory group aged <6 years, zero in the ambulatory group aged >=6 years, and zero among non-ambulatory participants. The numbers at risk for these serious-event summaries were 99, 177, and 36, respectively. The record lists one death in the group aged <6 years and zero deaths in each of the other groups.

For other adverse events, the record reports 84 affected participants among 99 at risk in the younger ambulatory group, 136 among 177 at risk in the older ambulatory group, and 20 among 36 non-ambulatory participants. These are counts of participants affected, not counts of distinct event episodes. The registry does not list top serious adverse-event terms.

These figures describe events recorded during study observation. They do not establish whether an event was caused by the disease, study procedures, or another factor. Because this was a natural history study rather than a treatment comparison, the counts should not be interpreted as evidence about the safety of a treatment. The record does not provide further detail about event definitions or follow-up completeness for these summaries.

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

The study was designed to describe the natural history of Duchenne muscular dystrophy in Chinese male participants, including the age at failure to walk. Its prospective, multicenter, single-cohort structure allowed participants to be observed over time, with visits planned every 6 months and follow-up described as 24-30 months. This design is suited to describing outcomes in the enrolled cohort, subject to the data collected and the limitations of follow-up.

The registry record identifies a Kaplan-Meier method and a median age with a 95% confidence interval for the primary endpoint. It also states that no participant in the ambulatory group aged <6 years had a failure-to-walk event during the study. However, the numerical median and confidence interval are not reported in the registry record. The primary endpoint's magnitude and precision therefore cannot be read from this record.

The absence of a reported event in that group does not establish a future outcome for those participants, nor does it establish a milestone age for the group. More generally, an observed natural history pattern is not a treatment effect. No randomized or separate control group is described, and no assigned treatment is listed.

The safety figures count participants with recorded adverse events during observation, including zero serious adverse events reported in each group and one death in the younger ambulatory group. They do not indicate cause, and they should not be treated as a comparative treatment-safety result.

The record also lists mutation, functioning, and quality-of-life outcomes, but does not provide their numerical results in the information available in the registry entry. These outcomes may describe different dimensions of disease history, yet their estimates and precision cannot be interpreted without reported results. The registry record supports understanding the study's design and planned outcome definitions, but not conclusions about unreported numerical outcomes.

13. Why This Trial Matters Statistically

Natural history studies can provide a structured account of outcomes over time in a defined patient population. This study focused on Chinese male patients with Duchenne muscular dystrophy and grouped participants by ambulatory status and age. Such descriptions can help characterize the kinds of outcomes a cohort study is designed to track, including a time-to-event milestone and measures of functioning and quality of life.

The primary endpoint illustrates why statistical methods must match the form of the outcome. Participants may experience the milestone at different ages, and some may not have a reported event before their last visit. Kaplan-Meier analysis is a general method for describing event-time data while retaining information from censored follow-up. The registry states that this method was used, and defines the event and censoring approach.

The record also demonstrates the importance of separating a planned analysis from a reported result. It identifies the primary summary as a median and 95% confidence interval, but does not report either number. Without those estimates, readers cannot assess the primary outcome's magnitude or precision from the registry entry. The stated absence of events in the youngest ambulatory group is informative about observed follow-up, but does not replace a numerical estimate for other groups.

Because the study had a single cohort and no randomized comparator, its role is descriptive rather than causal. The enrollment and follow-up structure, along with the registry's outcome definitions, make the intended scope clear. The listed secondary outcomes also show that natural history research may cover genetic, functional, and quality-of-life measures. Their numerical results, however, are not reported in the registry record.

14. 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 limitation for interpreting the central statistical question is that the registry record does not report the median age at failure to walk or its 95% confidence interval. It also does not report primary-endpoint event counts by group, the number analyzed, or follow-up distributions. The statement that no participant in the ambulatory group aged <6 years experienced the event indicates a sparse-event situation for that group, but the record gives no further group-specific estimation details.

The study is observational and single-cohort. There is no randomized assignment or separate control group, so the record cannot support a causal comparison of treatments. The participant groups are defined by age and ambulatory status, and the record does not provide adjusted comparisons or methods for addressing differences among groups.

Enrollment is recorded as 312, whereas the description gives an approximate target of 330 and approximate group targets. The registry does not report the reason for the difference between the recorded enrollment and the approximate target, nor does it provide the actual primary analysis count. The study description allows follow-up beyond Month 24 for some participants, but the record does not report participant-level follow-up or completeness.

The registry lists many secondary outcomes but zero analyses. Numerical results for these outcomes, multiplicity procedures, detailed missing-data handling, and sensitivity analyses are not reported in the registry record. The safety information gives participant counts, but does not provide event-level detail or establish causality. These limitations restrict interpretation to the study design, endpoint definitions, and the specific counts and observations stated in the record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Natural History Study In Chinese Male Patients With Duchenne Muscular Dystrophy — NCT03760029.
• Registry record last updated 2024-09-19; status last verified 2024-09.
• Results first posted 2024-09-19.
• 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.

18. Record Summary

This completed study was a multicenter, prospective, single-cohort natural history study of Chinese male patients with Duchenne muscular dystrophy. The registry records enrollment of 312 and describes approximate planned enrollment of 330. Observation was planned for 24-30 months, with visits every 6 months.

The primary outcome was age at failure to walk, analyzed using Kaplan-Meier methods, with participants without a caregiver-reported event censored at their last visit. The registry states that no participant in the ambulatory group aged <6 years had an event. The primary median and 95% confidence interval are not reported in the registry record.

There was no randomized comparison. The record lists 113 outcome measures and zero analyses. Safety counts include zero serious adverse events in each of the three groups and one death in the younger ambulatory group.