Effect of Proton Pump Inhibitors on CF Pulmonary Exacerbations: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Proton Pump Inhibitors on CF Pulmonary Exacerbations (NCT01983774), a randomized phase 2 study. The primary outcome is Time to First Pulmonary Exacerbation.

2. Clinical Question

The registry also names forced expiratory volume in one second, forced vital capacity and number of exacerbations as secondary outcomes. The primary endpoint focuses on when the first antibiotic-treated exacerbation occurred, rather than on a count of all exacerbations or a lung-function measurement. The registry record does not contain estimates that permit a numerical comparison of the groups on the primary outcome.

3. Trial Design

The registry describes a randomized, triple-masked, parallel-group phase 2 trial sponsored by Columbia University. The study status is completed. The recorded enrollment is 21. Arm-level records list 9 participants for esomeprazole and 8 for placebo; these entries are not a complete account of all enrolled participants, and the registry does not explain the difference between enrollment and the arm-level counts.

Participants assigned to esomeprazole received 40mg twice daily. The placebo was described as a matching sugar pill to esomeprazole 40mg twice daily. Random allocation is intended to make treatment assignment independent of participants’ prognostic characteristics on average. Masking is intended to limit bias related to knowledge of assignment, although the registry does not say who was masked or how masking was maintained. The parallel-group model means the assigned groups are compared over the study period rather than participants crossing between treatments, as a general description of this design.

The primary endpoint timeframe was 36 weeks. The study dates recorded in the registry are a start in 2008-02 and primary completion in 2011-08. These dates describe the study record and do not establish the duration of treatment for any individual participant. The registry does not report further details about treatment duration, follow-up procedures, adherence, allocation concealment or the method used to generate the random sequence.

The primary outcome was time to first pulmonary exacerbation, defined by need for oral or intravenous antibiotics. Secondary outcomes named in the registry were forced expiratory volume in one second, forced vital capacity and number of exacerbations. Although the registry identifies 4 outcome measures, arm-level results for the primary measure are unavailable. The registry record reports no posted analyses. It does not report the statistical analysis plan or a sample-size justification for the trial.

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: Twenty-one participants were assessed for eligibility. Of those, four were excluded (two did not meet inclusion criteria and two declined participation). Seventeen participants were randomized.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Values per arm for time to first pulmonary exacerbation cannot be reported. The data set was destroyed and no longer exists. The only available results exist as a figure within the study publication.

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 Time to First Pulmonary Exacerbation, measured over 36 weeks.

The primary endpoint was time to first pulmonary exacerbation, measured in weeks, over a timeframe of 36 weeks. The registry defines the event as the time to need for oral or intravenous antibiotics to treat a pulmonary exacerbation. This operational definition ties the endpoint to a treatment decision rather than to a symptom score or a lung-function measurement.

In general, a time-to-event endpoint captures both whether an event occurs during follow-up and how long it takes to occur. It can therefore distinguish patterns in which events arise sooner or later, even when a simple event count would not describe their timing. Such measures are often useful when the timing of a clinically important event is itself relevant. In this trial, the event definition was antibiotic treatment for an exacerbation.

The registry labels the endpoint as a mean with standard deviation, but it does not report the arm-level values. The record says the values cannot be reported because the data set was destroyed and that the only available results exist as a figure within the study publication. Consequently, a numerical estimate of the group contrast, its variability or its precision cannot be recovered from the registry record.

Time-to-event analyses can account for participants whose event timing is not observed in the same way, for example because follow-up ends before an event. In general, interpretation of those analyses depends on how follow-up and censoring are handled. Those details are not reported in the registry record. The absence of arm-level endpoint values also prevents a direct statistical assessment of the primary comparison from the registry results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical details in the registry are incomplete. It identifies a randomized parallel-group comparison and labels the primary measure as a mean with standard deviation, but the group means and standard deviations are missing. It reports no posted analyses. The statistical analysis plan, including the prespecified model, handling of missing observations and any adjustment variables, is not reported in the registry record.

What does a mean and standard deviation describe?

In general, a mean describes the average value of a continuous measure, while a standard deviation describes the spread of observations around that average. These summaries can help describe a group’s outcome distribution. For a time-to-event outcome, however, averages and standard deviations may not fully describe when events occur or how participants with no event by the end of follow-up are handled. Survival methods can use event timing and account for incomplete event observation under assumptions about censoring. The registry does not report which method, if any, was used for the primary comparison.

Because no mean or standard deviation is recorded for either arm, an unadjusted comparison cannot be recalculated from the registry summaries. No recalculated result is therefore available. The registry reports no discrepancy between its available information and an analysis, but this does not supply the absent primary-outcome estimates.

What would uncertainty measures add?

In general, a confidence interval communicates uncertainty around an estimated contrast. It can show whether the data are compatible with a range of effect sizes, rather than only presenting a single estimate. A p-value addresses a different question about data compatibility with a specified null model and assumptions; it does not measure the size or clinical importance of an effect. Neither a confidence interval nor a p-value for the primary comparison is reported in the registry record. Without an estimate and uncertainty measure, readers cannot assess statistical precision from this record.

How should planning illustrations be interpreted?

The registry describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between arms and a normal approximation. It describes the target effect as a stated fraction of the observed effect. Such calculations are planning scenarios, not observed trial findings and not observed power. The number of participants required in a future design depends on the assumed effect and other design choices; it is not evidence that the current study had a particular probability of detecting an effect. The registry does not report the trial’s own sample-size justification. Any planning values should therefore be read as illustrations under stated assumptions, not as a description of the trial’s design rationale.

For time-to-event planning, the registry says the illustrations use the total number of events, following the Schoenfeld approach. For other outcomes, the illustrations are expressed as participants per arm. The registry does not provide a primary-outcome effect estimate in the arm-level results, so a reader cannot independently assess that observed effect from these data. General planning calculations inherit the assumptions used to generate them and do not repair the missing outcome data.

Why does over-dispersion matter?

In general, over-dispersion occurs when outcome variability is greater than a statistical model assumes. If a model underestimates variability, standard errors may be too small and confidence intervals too narrow; inference can then appear more precise than warranted. This issue is especially relevant to counts when a simple model assumes the variance equals the mean. The registry names number of exacerbations as a secondary outcome, but does not report its distribution, model or analysis. There is no basis in the registry record to determine whether over-dispersion was assessed or relevant to that analysis.

For time-to-event outcomes, the methods also depend on how censoring, follow-up and any competing events are handled. In general, censoring means the exact event time is not observed during the available follow-up. Appropriate interpretation requires understanding how participants with incomplete event observation contributed to the analysis. Those methods and assumptions are not reported in the registry record. Since the primary data set was destroyed and the arm-level results are unavailable, the registry does not support a detailed audit or independent reproduction of the primary analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry names 4 outcome measures and identifies 3 secondary outcomes: forced expiratory volume in one second, forced vital capacity and number of exacerbations. When several outcomes are examined, the chance of finding at least one apparently unusual result can increase if each is tested separately without accounting for the number of tests. In general, multiplicity procedures can control error rates or distinguish a primary confirmatory question from supporting analyses. The registry does not report whether multiplicity was addressed, how outcomes were prioritized in the analysis, or whether the secondary outcomes were considered exploratory.

The registry reports no posted analyses, and numerical results for the primary endpoint are unavailable because the data set was destroyed. The record does not describe missing-data methods, the number of participants with missing outcome information, or reasons for missingness. It also does not report whether analyses used an intention-to-treat population, a per-protocol population or another analysis set. These omissions limit assessment of how participants with incomplete data or deviations from assigned treatment were handled.

The enrollment recorded is 21, while the arm-level records list 9 for esomeprazole and 8 for placebo. The registry does not explain this difference, so it should not be interpreted as evidence about withdrawals, exclusions or outcome completion. Further details about the analysis population and participant flow are not reported in the registry record. The primary outcome’s missing arm-level values prevent an assessment of whether missingness could have influenced the result.

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 0% reporting threshold.

The registry’s adverse-event entries report 0 serious adverse events among 9 participants at risk in the esomeprazole group and 0 among 8 at risk in the placebo group. It also records 0 for other adverse events in each group and 0 deaths in each group. These are the event counts recorded in the registry, not evidence that no adverse events of any kind occurred during the trial.

In general, a count of zero observed events does not establish that the underlying risk is zero. It indicates that no event in the specified category was recorded among the participants counted as at risk in this record. The amount of information about uncommon events is limited when the group counts are small; the registry’s safety entries do not provide confidence intervals or other uncertainty estimates. They also do not describe the event-collection procedures, follow-up duration for safety, or whether all events were captured consistently.

The record does not list serious adverse-event terms. The zero counts should be interpreted within the categories and participant counts recorded, without extending them to outcomes or time periods not described in the registry. These safety entries do not resolve the missing efficacy results for the primary endpoint.

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

This record can support a description of what the trial set out to compare: esomeprazole 40mg twice daily versus matching placebo in a randomized, triple-masked, parallel-group phase 2 study involving people with cystic fibrosis. It also specifies the primary endpoint as time to need for oral or intravenous antibiotics for a pulmonary exacerbation over 36 weeks. These details clarify the research question and how the primary event was defined.

The record cannot support a numerical conclusion about the primary comparison. The arm-level outcome values are unavailable because the data set was destroyed, and the registry says the only available results exist as a figure within the study publication. No effect estimate, confidence interval or p-value for the primary comparison is reported in the registry record. The objectives described in the study summary are not results, and the study’s completed status does not establish whether the intervention changed the outcome.

Likewise, the named secondary outcomes do not reveal whether lung function or exacerbation counts differed between groups. No posted analyses are recorded, and numerical secondary results are not present in the registry information. The registry’s adverse-event counts are descriptive entries for the recorded categories; they do not establish absence of all harms or quantify the uncertainty around event rates.

In general, a trial result is interpreted by considering the estimated effect, its precision, the endpoint definition and the analysis methods. Here, the missing primary outcome values and unreported statistical methods prevent those elements from being evaluated using the registry record alone. The result is therefore not a numerical estimate of benefit or harm; it is a record of the study question and a clear limitation on what can be concluded from the posted registry data.

13. Why This Trial Matters Statistically

This trial is statistically notable because its registry record preserves a specific primary endpoint and randomized comparison while lacking the underlying arm-level outcome results. A design can be described clearly, but that description cannot substitute for the observed data. Without estimates and uncertainty measures, readers cannot assess the magnitude, direction or precision of the primary comparison from the registry record.

The endpoint also illustrates why outcome definitions matter. The primary event was not simply any respiratory infection: it was the time to need for oral or intravenous antibiotics to treat a pulmonary exacerbation. Different operational definitions can capture different clinical events, so the definition helps clarify what the planned comparison concerns. The registry’s secondary outcomes—lung-function measures and exacerbation counts—represent distinct questions and cannot be treated as interchangeable evidence for the primary endpoint.

For biostatisticians and clinical researchers, the missing outcome values highlight the importance of preserving analyzable data and documenting the analysis. Without the data set, reported estimates, analysis population and method details, independent reproduction and scrutiny are limited. The registry states that a figure in the study publication is the only available result, but its own record does not provide the numerical values needed for a direct assessment.

The case also underscores the distinction between planning and evidence. Sample-size illustrations based on an observed effect are hypothetical planning aids under specified assumptions; they are not observed power and do not substitute for reporting the trial’s estimates. The registry does not report the trial’s own sample-size justification. The statistical importance of the record is therefore less about a demonstrable treatment effect and more about how reporting, data retention and transparent methods determine whether a completed trial can be evaluated quantitatively.

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 central limitation is that the primary outcome data are unavailable in the registry record. The record states that values per arm cannot be reported because the data set was destroyed, and that the only available results exist as a figure within the study publication. It does not provide numerical estimates or uncertainty measures for the primary endpoint. This prevents independent recalculation and limits assessment of the observed effect.

Important design and analysis details are also absent. The registry does not report the statistical analysis plan, the method used to compare time to first exacerbation, how censoring or incomplete follow-up was handled, or the analysis population. Missing-data procedures, adherence information, allocation concealment and the roles covered by triple masking are not reported in the registry record. The record does not explain the relationship between enrollment of 21 and the arm-level counts of 9 and 8.

Although secondary outcomes are named, the registry does not provide numerical results for them in the available information, and it reports no posted analyses. Multiplicity handling and a sample-size justification are not reported. The safety entries contain event counts but do not provide uncertainty estimates or detailed ascertainment methods. These limitations mean that the registry record is insufficient for a full evaluation of efficacy, safety, precision or robustness. They should not be filled by assumptions about the protocol or analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Proton Pump Inhibitors on CF Pulmonary Exacerbations — NCT01983774.
• Registry record last updated 2022-02-17; status last verified 2022-01.
• Results first posted 2022-02-17.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry describes a completed randomized, triple-masked, parallel-group phase 2 trial sponsored by Columbia University. It compared esomeprazole 40mg twice daily with matching placebo in people with cystic fibrosis. Recorded enrollment was 21.

The primary endpoint was time to first pulmonary exacerbation, defined as time to need for oral or intravenous antibiotics, over 36 weeks. The registry names forced expiratory volume in one second, forced vital capacity and number of exacerbations as secondary outcomes.

Arm-level primary outcome values are unavailable because the data set was destroyed. The registry says the only available results exist as a figure within the study publication. It reports no posted analyses, and the statistical analysis plan and sample-size justification are not reported in the registry record. Adverse-event entries report 0 serious events and 0 deaths in each group, alongside 0 other adverse events in each group.