Hereditary Haemorrhagic Telangiectasia Flight Safety Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Hereditary Haemorrhagic Telangiectasia Flight Safety Study (NCT01590121), a registered phase not stated study. The primary outcome is HHT Patients Who by the Questionnaire Did or Did Not Self Report a Medical Complication During Flight.

2. Clinical Question

The rationale in the record is that HHT involves abnormal blood vessels and can be associated with bleeding and low blood oxygen levels, particularly when the lungs are affected. The investigators wanted to know whether people with HHT reported more problems during flights than on land. The questionnaire focused on past flights, rather than assigning participants to a flight or other exposure.

The record describes the intended question but does not report a direct estimate comparing complications on flights with complications on land. Its listed primary measure is the percentage of individuals reporting complications during flight. Without an outcome count or percentage, the registry does not establish how frequently respondents reported complications, nor how precise that estimate would be.

3. Trial Design

This completed study was registered as the Hereditary Haemorrhagic Telangiectasia Flight Safety Study, NCT01590121. Imperial College London is listed as the sponsor. The record gives a start date of 2010-01 and a primary completion date of 2011-10. Enrollment is listed as 156.

The study was questionnaire-based and asked people with HHT to describe their past flight experience. The listed study activities are aeroplane flight in the past, with no active intervention for the study, and a questionnaire. Participants were asked to report flights taken up until questionnaire completion. The record describes the flight-history age range as aged 18-90 (mean 55)ys. It states that 145 HHT-affected respondents had flown for 18,943 hours over 3,950 flights.

The primary outcome description limits the comparison to people who had taken a flight, whether long haul or short haul. It frames the comparison as whether participants did or did not suffer a flight complication. The listed outcome is a percentage of patients, and the description identifies self-reported medical complications as the subject of the measure.

This design records participants’ reports about prior experience; it does not assign a flight exposure or an active treatment. Allocation is not stated, and the registry notes that the study is not a randomized comparison. The record does not describe a separate control arm or a protocol for matching flight and land observations. Consequently, the question and endpoint should be understood as descriptive of reported flight experiences, not as a randomized test of an intervention.

The registry lists one outcome measure and no analyses. It does not report the questionnaire completion rate, a detailed recruitment method, the number of people who did not fly, or a statistical analysis plan. Although enrollment is listed as 156, the record does not explain how that figure relates to the 145 respondents who had flown.

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

Analysis population for the primary outcome, as defined in the registry: Percentage of individuals who reported complications

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 HHT Patients Who by the Questionnaire Did or Did Not Self Report a Medical Complication During Flight, measured over Patient were asked to report all flights taken up until questionnaire completion aged 18-90 (mean 55)ys. 145 HHT-affected respondents had flown for 18,943 hours over 3,950 flights..

The primary endpoint is the percentage of individuals with HHT who reported a medical complication during flight. The registry describes the eligible comparison group as patients who had taken a flight and says participants were classified according to whether they did or did not suffer a flight complication. The measure is therefore a binary, participant-level outcome: a respondent either reports a complication or does not report one.

A percentage can describe how common the reported outcome was among the people included in the endpoint analysis. The record states that the intended uncertainty measure is a 95% confidence interval. In general, a confidence interval communicates the statistical precision of an estimate: narrower intervals indicate greater precision, while wider intervals indicate more uncertainty. The registry record does not report the endpoint percentage, the number reporting a complication, or the confidence interval, so neither the observed frequency nor its precision can be assessed from the recorded results.

The participant-level measure is not the same as a rate per flight or per hour of flying. The record gives a total of 3,950 flights and 18,943 hours among 145 HHT-affected respondents who had flown, but it does not specify that the primary endpoint uses flights or hours as its denominator. A participant reporting any complication and a count of complications across flights answer different questions. The registered endpoint is framed as the percentage of patients reporting complications, not as an event rate per flight.

Self-report is relevant to a study of personal flight experience, but depends on participants’ recall and on how they understood and answered the questionnaire. The record does not report a definition or severity threshold for a flight complication. It also does not report whether complications were independently confirmed. These details would be important for interpreting exactly what a positive response represents.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant-level percentage represent?

The primary measure is a percentage of patients reporting a complication during flight. In general, a binary endpoint assigns each participant to a response category, such as reporting a complication or not reporting one. A percentage summarizes how common one category is among the participants included in the analysis. Its interpretation depends on the denominator: the people included in the endpoint calculation must match the population the result is meant to describe.

The registry says that the primary comparison was limited to patients who had taken a flight. It also reports that 145 HHT-affected respondents had flown. But it does not report how many of these respondents had a usable answer to the complication question or how many reported a complication. The participant-level percentage cannot be reconstructed from the exposure totals alone. In particular, the count of flights and the number of flight hours are not substitutes for a count of people with the endpoint.

How should a confidence interval be understood?

The record identifies a 95% confidence interval as the intended measure of dispersion for the primary endpoint. In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the statistical procedure. It does not describe the range of individual participant experiences, and it does not guarantee that the true value lies within a particular interval. Its width is affected by the amount of information and by the method used to calculate it.

No interval or endpoint estimate is reported in the registry record. As a result, the precision of the planned percentage cannot be evaluated. A point estimate alone, if it had been reported, would not answer how uncertain it was; conversely, a confidence interval without a clearly defined analysis population would also be difficult to interpret.

Why do the units of analysis matter?

The record gives three kinds of exposure information: respondents, flights, and hours. These units are not interchangeable. The primary endpoint is defined as a percentage of patients. A flight-level analysis would instead count flights with complications, and a rate based on hours would use time at risk as its exposure. Those approaches answer different questions and can produce different interpretations.

There can also be dependence among repeated observations from the same person: flights taken by one participant are not necessarily statistically independent of one another. In general, treating clustered observations as if they were unrelated can understate uncertainty. A method for analyzing flights as repeated observations would need to account for that dependence. The registry does not report a flight-level analysis or an approach to within-person clustering. This concern should not be imposed on the listed participant-level endpoint unless the analysis actually treats flights as separate outcome observations.

What can be inferred from the questionnaire design?

Because participants reported on past flights, the endpoint reflects questionnaire responses rather than prospective monitoring described in the record. Self-report is a direct way to capture a person’s account, but it can be affected by memory, interpretation of the question, and willingness to report an experience. The registry does not report the wording of the complication question, a clinical definition of complication, or an independent verification procedure. Without those details, the meaning and consistency of a reported complication cannot be fully assessed.

The design also lacks a reported randomized comparator. The registry describes a comparison between people who did and did not report a flight complication, not a randomized allocation between flight and no flight. General statistical interpretation must therefore distinguish description from causal inference. A questionnaire describing prior flights does not, by itself, establish that flying caused a reported problem or that flight experiences differ from land experiences.

What does the record say about analysis and planning?

The registry lists one outcome measure and no analyses. It does not report a statistical analysis plan, a model, any adjustment variables, or a hypothesis test for the primary endpoint. The endpoint field’s reference to a confidence interval describes the intended dispersion measure; it does not provide a calculation method or an observed interval.

The record also distinguishes planning illustrations from the study’s own design: its sample-size assumptions describe illustrations based on an observed effect, with equal allocation, a two-sided significance level of 0.05, and a normal approximation. Such illustrations are not evidence that the study had a particular observed power, and they are not a substitute for the protocol’s sample-size justification. The protocol’s sample-size justification is not reported in the registry record. Since the primary endpoint result is also absent, the record does not give a reported observed effect from which to judge the relevance of those illustrations.

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("HHT Flight Group")
n      <- c(145)
events <- c(112)
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  HHT Flight Group  145  112  77.2  69.5  83.8  69.8  83.3  69.7  83.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, a percentage of patients reporting a medical complication during flight, and lists no analyses. It does not report whether additional outcomes were collected outside the registry entry, whether multiple statistical tests were planned, or whether any adjustment for multiple comparisons was used. A multiplicity strategy is therefore not reported in the registry record. With no posted analyses or test results, there is no basis for assessing how multiplicity may have affected statistical inference.

Missing-data handling is also not described. The record does not state how incomplete questionnaires, unanswered complication questions, or ambiguous answers were treated. It does not give the number of questionnaires returned or the number of respondents with a usable answer to the primary outcome. The reported 145 HHT-affected respondents who had flown should not be assumed to be the endpoint denominator, because the record does not explicitly state that every one of them provided a usable complication response.

The relationship between the enrollment figure of 156 and the 145 respondents who had flown is not explained. The record does not report whether people who had not flown, people who did not respond, or people with incomplete responses were excluded from the primary endpoint analysis. Without those details, the potential for selection or missing-data bias cannot be assessed.

The analysis population is described only in broad terms as patients who had taken a flight. The registry does not report an intention-to-treat population, a per-protocol population, or any other formally specified analysis set. It also does not state how participants with more than one flight were represented in the primary analysis. These omissions matter because the denominator and rules for handling repeated or incomplete observations affect the interpretation of a percentage.

12. 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 0% reporting threshold.

The registry’s adverse-event entry lists zero serious events, zero other events, and zero deaths for the group titled “Pateints With Hereditary Haemorrhagic Telangiectasia.” The record lists 156 as at risk for each adverse-event category. These are registry adverse-event figures and should be read within that reporting context.

Those entries do not establish that no participant ever experienced a flight complication. The primary endpoint is a questionnaire measure of self-reported medical complications during flight, while the adverse-event fields are a separate registry summary. The record does not say that the adverse-event categories capture every complication reported in the questionnaire, nor does it explain how the two sets of information were reconciled.

The adverse-event figures also do not provide information about severity, timing, or relationship to a particular flight beyond the categories shown. No serious adverse-event terms are listed. The appropriate interpretation is limited: the registry reports zero affected in the listed serious and other adverse-event fields and zero deaths, while the primary self-reported flight-complication result is not reported in the registry record.

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

This study addresses a practical descriptive question about the experiences of people with HHT who had flown. Its questionnaire approach records participants’ accounts of past air travel, and the record documents substantial reported flight exposure among respondents who had flown: 145 HHT-affected respondents, 18,943 hours, and 3,950 flights. Those details provide context for the study but do not reveal how many people reported a complication.

The registry identifies the primary endpoint as the percentage of patients who did or did not self-report a medical complication during flight. However, the percentage, event count, and confidence interval are not reported in the registry record. Consequently, the endpoint cannot be used to quantify the frequency of reported complications or the precision of that estimate.

The record’s rationale refers to whether problems are increased on flights compared with on land. The listed outcome does not provide a reported flight-versus-land comparison, and the record does not describe a like-for-like control group. It therefore cannot establish a comparative difference between those settings. Nor does a questionnaire about past experiences by itself establish that flying caused any reported complication.

The study’s self-report method can capture experiences that participants consider important, but interpretation depends on recall, question wording, and the definition of a complication. Those details are not reported. The record also does not explain the relationship between enrollment and respondents who had flown, or how missing questionnaire answers were handled.

In short, the registry communicates the study’s question, design, and flight-exposure context, but not its primary result. The adverse-event entries are not a replacement for that result. No conclusion about the occurrence, absence, or comparative frequency of flight complications can be drawn from the missing endpoint estimate.

14. Why This Trial Matters Statistically

Statistically, the study illustrates why an endpoint’s denominator and unit of analysis must be clear. The primary outcome is a percentage of patients, while the record also gives the number of flights and hours. A participant-level percentage describes the proportion of people reporting a complication; it does not describe the proportion of flights affected or a rate per hour. Keeping these quantities distinct prevents a descriptive measure from being interpreted as a different kind of risk.

The study also highlights the importance of reporting both an estimate and its uncertainty. A planned 95% confidence interval would help readers judge the precision of the percentage, but neither the interval nor the percentage is reported. Without those results, the registry cannot support a quantitative interpretation of the primary question.

Questionnaire studies bring additional statistical concerns. Responses can depend on recall and on how respondents interpret the question, and incomplete responses can change the population represented by an estimate. The record does not report questionnaire completion, missing-data handling, or the endpoint denominator. These are not minor reporting details: they are necessary to understand who contributes to the estimate and what the estimate represents.

Finally, the study rationale raises a comparative question about flights and land, while the listed primary endpoint describes reports of complications during flights. A comparison needs outcome information from both settings under a clearly described design. The registry record does not report such a comparison. Distinguishing the motivating question from the endpoint actually reported is central to interpreting what a study can answer.

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 primary limitation for interpreting the registry entry is that the primary endpoint result is not reported. The endpoint is described, but the registry gives no complication count, percentage, or confidence interval. The completed status and the recorded flight exposure do not fill that gap.

The measure relies on participants’ recollection and self-report about past flights. The registry does not provide the questionnaire wording, a clinical definition of a complication, or information on independent confirmation. It therefore remains unclear how consistently respondents may have interpreted the outcome and whether reports were verified.

The record does not report a direct comparison with experiences on land, despite that comparison appearing in the study rationale. It also does not describe a separate control group. The registry notes that the study was not a randomized comparison and that allocation was not stated, so causal or comparative interpretation is not supported by the listed design.

Several details needed to assess representativeness are absent. The record does not state how many people were sent the questionnaire, how many returned it, or how many had a usable response to the primary question. It lists enrollment as 156 and reports 145 HHT-affected respondents who had flown, but does not explain the relationship between these figures. Missing-data procedures and the formal analysis population are not reported.

The record gives exposure totals for people, flights, and hours, but does not say how multiple flights per person were handled in an analysis. The primary endpoint is participant-level, so the flight totals alone do not supply its denominator. No statistical analysis plan or analysis results are listed. Together, these reporting gaps limit assessment of precision, potential selection effects, and the scope of the study’s conclusions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Hereditary Haemorrhagic Telangiectasia Flight Safety Study — NCT01590121.
• Registry record last updated 2024-11-12; status last verified 2024-09.
• Results first posted 2024-11-12.
• 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

NCT01590121 is a completed questionnaire-based study sponsored by Imperial College London. The record lists a start date of 2010-01, primary completion of 2011-10, and enrollment of 156. It concerns people with hereditary haemorrhagic telangiectasia and asks about complications reported during past flights.

The primary endpoint is the percentage of patients who did or did not self-report a medical complication during flight. The record states that 145 HHT-affected respondents had flown for 18,943 hours over 3,950 flights. It lists one outcome measure and no analyses.

The registry does not report the primary endpoint estimate or its confidence interval. It also does not report a direct flight-versus-land comparison, questionnaire completion details, or missing-data handling. Adverse-event fields list zero affected for serious and other events and zero deaths, but those entries do not replace the missing questionnaire outcome.