This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for : TRANSITION: An Observational Study of Transition From Lumacaftor/Ivacaftor to Tezacaftor/Ivacaftor (Tez/Iva) (NCT03445793), a registered phase not stated study. The primary outcome is Change in Sweat Chloride Concentration in Millimoles/Liter From Baseline at 6 Months Pre-specified to be Reported.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03445793 |
| Phase | Phase not stated |
| Condition | Cystic Fibrosis (CF) |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Jewish Health |
| Results posted | Yes |
2. Clinical Question
Population
People aged ≥ 12 with cystic fibrosis who were transitioning from Orkambi, the lumacaftor/ivacaftor treatment, to tezacaftor/ivacaftor. The study was a single-center observational study, with enrollment of 5 participants.
Intervention
The treatment transition being observed was from lumacaftor/ivacaftor to tezacaftor/ivacaftor. The registry describes measurements at baseline and at 1 month, 3 months, and 6 months after initiation of tezacaftor/ivacaftor.
Comparator
No concurrent comparison group is reported. Each participant’s baseline was the reference for the planned change measurements; that within-person reference is not a randomized control group.
Primary question
What was the average change in sweat chloride concentration from baseline to 6 months after the transition? The registry record identifies this as the primary outcome, but the result and its confidence interval are not reported in the registry record.
The study addressed a clinical transition in routine treatment rather than a randomized assignment between two treatments. Its stated focus was the change in sweat chloride, with clinical and laboratory outcomes also assessed over approximately 6 months of participation. The description says that change from baseline at 6 months was prespecified for reporting. However, no primary-outcome estimate, uncertainty interval, or analysis result is reported in the registry record. Consequently, the stated question can be described, but its answer cannot be characterized from the registry results.
3. Trial Design
This was a completed, single-center observational study sponsored by National Jewish Health. The registry lists enrollment of 5 people with cystic fibrosis and describes participants aged ≥ 12 who transitioned from Orkambi to tezacaftor/ivacaftor. The study start date is 2018-03-01 and the primary completion date is 2019-11-01. The record describes participation lasting approximately 6 months.
Clinical and laboratory measurements were planned at baseline and 1 month, 3 months, and 6 months after starting tezacaftor/ivacaftor. The primary outcome was change in sweat chloride concentration from baseline at 6 months. The registry also lists secondary outcomes concerning the reasons for transition, pulmonary exacerbations, lung function, respiratory quality-of-life score, weight, body mass index, and fecal elastase measurements. It states that several changes from baseline at 6 months were prespecified for reporting.
The study is observational, and the record does not identify a randomized allocation or a parallel control arm. Baseline measurements provide a before-transition reference, but they do not make the study a like-for-like comparison of treatments. Changes after transition can be described over time, but this design alone cannot separate the transition from other changes occurring during follow-up.
The registry lists 10 outcome measures and 0 analyses. Although the study status is completed, outcome estimates and analysis details are not reported in the registry record. The statistical plan, including any prespecified modeling approach, handling of repeated measurements, and analysis population definitions, 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: Participant must complete baseline visit while on lumacaftor/ivacaftor prior to transition to tezacaftor/ivacaftor.
Overall Study
| Stage | Observational |
|---|---|
| STARTED | 5 |
| COMPLETED | 5 |
| NOT COMPLETED | 0 |
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.
| Characteristic | Unit | Observational |
|---|---|---|
| Participants analysed | 5 | |
| Age, Continuous | years | 28.4 (SD 1.14) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 3 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 5 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Cystic Fibrosis Mutation Type: Homozygous for F508del | Participants | 5 |
| Cystic Fibrosis Mutation Type: Heterozygous for F508del | Participants | 0 |
| BMI | kg/m^2 | 22.3 (SD 1.50) |
6. Primary Endpoint
The registry lists the primary outcome as Change in Sweat Chloride Concentration in Millimoles/Liter From Baseline at 6 Months Pre-specified to be Reported, measured over Baseline to 6 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | mmol/L |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in sweat chloride concentration, measured in millimoles per liter, from baseline to 6 months. The registry describes the endpoint as an average change and specifies a mean with a 95% confidence interval. Its description refers to the average change at 6 months relative to baseline.
Sweat chloride is used as a measure of cystic fibrosis transmembrane conductance regulator function. In general, a biomarker endpoint can provide a measurable laboratory outcome over a defined period, while clinical outcomes describe other aspects of participants’ health and experience. The use of a mean summarizes the average observed change across the analyzed participants; it does not imply that every participant had the same change.
A confidence interval communicates uncertainty around an estimated mean. In general, a narrower interval indicates greater precision, while a wider interval indicates less precision. The registry record does not report the mean change or its confidence interval, so the magnitude, direction, and precision of the primary endpoint cannot be assessed from the posted results. The registry’s description of the endpoint establishes what was intended to be measured, not what the study found.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record defines a specific primary question: the average change in sweat chloride concentration from baseline at 6 months after a treatment transition. It does not report an estimate for that change, a confidence interval, or a statistical test result. Thus, there is no posted primary-outcome result from which to describe either the direction or size of the observed change, or its precision.
The record lists 5 participants enrolled and marks the study as completed. Completion and enrollment do not establish that every participant contributed a six-month measurement, and the number with an observed primary endpoint is not reported in the registry record. The analysis population and the handling of any unavailable measurements are also not reported in the registry record. Those details matter because a mean and its confidence interval depend on which observations were included.
The study’s observational structure is central to interpretation. Participants transitioned from one treatment to another; the record does not describe random allocation or a concurrent control group. A comparison of follow-up values with baseline can describe change over time in the observed participants, but it cannot by itself establish that the treatment transition caused any change. Other influences during follow-up cannot be ruled out on the basis of the registry description.
The secondary outcomes broaden the intended assessment to pulmonary exacerbations, percent-predicted FEV1, the CFQ-R respiratory domain, weight, body mass index, fecal elastase, and reasons reported by physicians and participants for the transition. These outcomes are listed, but their results are not reported in the registry record. The record therefore does not support a statistical comparison across those outcomes or a conclusion about consistency between laboratory and clinical measures.
Safety figures are reported separately: the observational group lists 5 people at risk, 3 affected by serious events, 2 affected by other events, and 0 deaths. The most frequently listed serious-event term is hospitalization due to pulmonary exacerbation, at 60.0%. These counts describe the small observed cohort; they do not supply a controlled comparison or establish attribution to the transition.
Any recalculated quantities based on posted summaries would be unadjusted calculations rather than the sponsor’s analysis. In this record, no analysis results are listed, so no primary estimate or recalculated estimate can be interpreted. Planning illustrations based on an observed effect, where displayed, are not observed power and should not be read as results or as the study’s original design justification.
9. Statistical Methods Explained
What does the mean change represent?
The registry specifies the primary measure as a mean change in sweat chloride concentration from baseline to 6 months. In general, a mean is a summary of the measured changes among the observations included in an analysis. It describes the average and does not show the range of individual participant changes or whether those changes were similar. The registry record does not report the numerical mean, the number of participants contributing to it, or individual-level results.
The endpoint description refers to the average change at 6 months. The exact computational details, such as how measurements were handled when a participant had more than one value in a time window, are not reported in the registry record. The record also does not specify whether the estimate was adjusted for any covariates or how the repeated measurements were modeled. Those details should not be inferred from the endpoint name alone.
How should a confidence interval be read?
The registry names a 95% confidence interval as the dispersion measure for the primary mean. In general, a confidence interval expresses uncertainty about an estimated quantity under the assumptions of the method used. It communicates the range of values reasonably compatible with the data and method, rather than the spread of individual measurements. It is not a guarantee that the true value lies within any one calculated interval.
Precision depends on the amount and variability of information available. In general, a small cohort can yield an imprecise estimate, but the width of an interval cannot be inferred from enrollment alone. Here, neither the primary estimate nor its interval is reported in the registry record. Accordingly, no statement about precision can be made from the registry results.
What can an observational before-and-after design establish?
In general, measuring participants before and after a transition describes how their measured outcomes changed over the observation period. Using each person’s baseline as a reference can account descriptively for the fact that participants start at different values. However, without a randomized comparison group, a change over time cannot be attributed uniquely to the transition. The registry does not report a control group or a randomized allocation.
The stated schedule includes baseline, 1 month, 3 months, and 6 months. Repeated measurements can help describe the time course, but the registry record does not report how those repeated observations were analyzed. It does not say whether the primary analysis used only baseline and 6-month values or incorporated intermediate measurements, nor does it describe a model for within-person correlation.
What do the planning illustrations mean?
In general, sample-size planning calculations describe how many participants might be needed under specified assumptions to detect a chosen effect with a chosen statistical power. The planning assumptions associated with this study describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. For time-to-event calculations, the stated convention is a total number of events; other planning results are expressed as participants per arm for 80% power or another stated power level.
These are planning illustrations based on an observed effect, not the study’s own design justification. The registry record does not report a sample-size justification, and it does not report an observed effect for the primary outcome. Planning values are hypothetical requirements under their assumptions, not observed power. They also do not convert this observational study into a two-arm randomized comparison.
What does the analysis record show?
The registry lists 0 analyses. It does not report a primary outcome estimate, test statistic, p-value, or confidence interval. A statistical plan, including any interim analyses, is not reported in the registry record. No analysis method should therefore be attributed to the sponsor beyond the endpoint summary expressly named in the record: a mean with a 95% confidence interval.
General statistical interpretation requires attention to the estimate, its uncertainty, the analysis population, and the design. Here, the outcome definition and broad measurement schedule are described, but the numeric estimate and several analysis details are absent. This limits interpretation to the intended question and the small set of reported safety counts.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple secondary outcomes alongside the primary sweat chloride endpoint. When many outcomes are assessed, general statistical practice recognizes that the chance of finding at least one apparently unusual result can increase if each is tested separately without accounting for multiplicity. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a plan distinguishing confirmatory from exploratory analyses. It is therefore not possible to determine how multiple outcomes were intended to be interpreted statistically.
Missing-data methods are not reported in the registry record. The record specifies measurement times but does not state how absent measurements, withdrawals, or incomplete follow-up were handled. Enrollment of 5 does not establish how many participants contributed data at each visit or to the six-month endpoint. No imputation method or sensitivity analysis is reported.
Analysis populations are also not defined in the registry record. It does not identify whether the primary analysis included all enrolled participants, only those with available six-month measurements, or another group. These omissions prevent assessment of how the analyzed participants may differ from the enrolled group. Interim analyses and stopping rules are not reported in the registry record. The absence of these details should be treated as an absence of reporting, not evidence that a particular procedure was or was not used.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Observational | 3 | 5 | 60.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Observational | 0 of 5 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Observational | 2 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | Observational |
|---|---|---|
| Hospitalization due to pulmonary exacerbation | Respiratory, thoracic and mediastinal disorders | 3 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Observational |
|---|---|---|
| Increased cough after stopping Tezacaftor/Ivacaftor | Respiratory, thoracic and mediastinal disorders | 1 of 5 |
| Exacerbation of Chronic Sinusitis | Respiratory, thoracic and mediastinal disorders | 1 of 5 |
Serious events with the highest arm-level rate: hospitalization due to pulmonary exacerbation (60.0%).
The registry reports safety information for an observational group with 5 people at risk. It lists 3 people affected by serious adverse events, 2 affected by other adverse events, and 0 deaths. The most frequently listed serious-event term is hospitalization due to pulmonary exacerbation, reported as 60.0%.
These figures are descriptive counts from the study group. The registry record does not provide a concurrent comparison group, event-level timing, or an analysis attributing events to the treatment transition. The serious-event term is a registry classification and should not be read as proof that the transition caused the event. The record also does not provide further detail about event severity, duration, recurrence, or participant overlap between the serious and other event categories.
With enrollment of 5, the safety figures describe a small cohort and do not establish how frequently such events would occur in a broader population. The record reports 0 deaths, which describes the recorded study group; it is not a statement about risk outside the study.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a small observational study was designed to follow people with cystic fibrosis transitioning from lumacaftor/ivacaftor to tezacaftor/ivacaftor. It specifies sweat chloride change from baseline at 6 months as the primary outcome and lists a schedule of measurements at baseline, 1 month, 3 months, and 6 months. These details define the study question and the intended follow-up, but do not provide an answer to the primary question.
The primary numerical result is not reported in the registry record. Without a mean change and confidence interval, the direction, magnitude, and precision of any change in sweat chloride cannot be described. Secondary outcome results are also not reported in the registry record. The listed outcomes indicate what the study intended to assess, not what was observed.
Even if within-person changes were available, the observational design would support description of change during follow-up rather than a controlled causal conclusion. No concurrent comparator or random assignment is reported. Other factors occurring over time could contribute to measured change, and the registry record does not provide a design that isolates the effect of the transition.
The safety record reports event counts for the five-person group, including serious events and deaths. Those descriptive figures do not establish comparative safety or causation. Overall, the registry contains a defined clinical question and limited cohort-level safety information, but does not contain the outcome analyses needed to judge the primary endpoint or the secondary outcomes.
13. Why This Trial Matters Statistically
Statistically, the record is useful for distinguishing a clearly named endpoint from a reported result. It identifies mean change in sweat chloride at 6 months and specifies a confidence interval as the measure of uncertainty. Yet the outcome estimate and its uncertainty are not reported in the registry record. A well-defined estimand does not substitute for a posted analysis.
The study also illustrates the interpretive limits of a small observational cohort. Five participants were enrolled, and the design follows people through a treatment transition rather than assigning them to randomized groups. Such data can describe individual or average change if results are reported, but they do not by themselves identify the transition as the cause of that change. The lack of a concurrent comparator is especially important when interpreting before-and-after measurements.
The listed secondary measures span laboratory, lung-function, quality-of-life, anthropometric, and event outcomes. This breadth can be informative when results and a multiplicity plan are available. Here, neither secondary outcome results nor such a plan are reported in the registry record. The example therefore underscores why readers need both outcome estimates and analysis context, including the number analyzed and the approach to missing observations.
Finally, planning calculations should remain separate from evidence about observed outcomes. Sample-size illustrations based on an observed effect are not an estimate of the treatment effect, are not observed power, and do not replace the missing analysis. The record’s main statistical contribution is its specification of what was intended to be measured; its posted results do not permit an efficacy or precision assessment.
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.
Several limitations follow directly from the registry record. Enrollment was 5, and the study was single-center and observational. No randomized assignment or concurrent comparator is reported. These features limit the ability to distinguish change associated with the treatment transition from change due to other influences during follow-up, and they constrain how broadly cohort observations can be interpreted.
The primary endpoint result is not reported in the registry record, despite the stated plan to report change at 6 months. The number of participants with a six-month measurement is not reported. Neither the primary estimate nor its 95% confidence interval is available, and secondary outcome results are not reported. The analysis population and handling of missing measurements are not reported in the registry record.
The record does not describe the statistical analysis plan, model for repeated measurements, interim analyses, sample-size justification, or approach to multiplicity. It also does not provide enough detail to assess whether planned measurements were collected as scheduled or how outcome definitions were operationalized. These are reporting gaps; they should not be filled by assuming a particular procedure.
The safety information is limited to counts and a listed serious-event term. Timing, event-level details, attribution, and a comparison group are not reported. Accordingly, the safety data are descriptive rather than comparative. Together, these limitations mean that the registry supports a description of the study’s purpose and design, but not an estimate of the primary outcome or a causal conclusion.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: : TRANSITION: An Observational Study of Transition From Lumacaftor/Ivacaftor to Tezacaftor/Ivacaftor (Tez/Iva) — NCT03445793.
- Registry record last updated 2024-01-23; status last verified 2024-01.
- Results first posted 2021-10-01.
- 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.
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18. Record Summary
NCT03445793 is a completed, single-center observational study sponsored by National Jewish Health. It enrolled 5 people with cystic fibrosis who transitioned from lumacaftor/ivacaftor to tezacaftor/ivacaftor. The registry describes measurements at baseline and 1 month, 3 months, and 6 months.
The primary outcome was mean change in sweat chloride concentration from baseline at 6 months, with a 95% confidence interval specified. The registry lists 10 outcome measures and 0 analyses. The primary and secondary outcome results are not reported in the registry record.
For the observational group, the record lists 5 people at risk, 3 affected by serious events, 2 affected by other events, and 0 deaths. Hospitalization due to pulmonary exacerbation is the most frequently listed serious-event term, at 60.0%.