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 Enhancement of Corticosteroid Efficacy in COPD (NCT02340520), a na phase 3 study. The primary outcome is Bronchodilation.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02340520 |
| Phase | Phase 3 |
| Condition | COPD |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 13 |
| Arms in the primary outcome | n/a |
| Lead sponsor | UConn Health |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns subjects with COPD described in the brief summary as nonresponsive to bronchodilators. The registry lists COPD as the condition and records enrollment of 13. The brief summary describes a pilot study planned for 10 subjects; the relationship between that planned number and the recorded enrollment is not explained in the registry record.
Intervention
Participants received theophylline tablets for 1 week. Roflumilast was then added to theophylline for a further 1 week. The study description links this sequence to measurements of circulating HDAC levels and examination of the bronchodilator response to inhaled beta agonist after acute oral prednisone.
Comparator
There is no separate control group described. The listed design is single-group, with allocation recorded as NA and masking recorded as none. Measurements at baseline, Week 1 and 2 provide observations at different stages of the treatment sequence, but they are not a like-for-like comparison with an untreated or separately treated group.
Primary question
The registered primary outcome, titled Bronchodilation, concerns change in FEV1 and FVC measured in liters. The study asks whether lung-function measurements and the bronchodilator response change during the sequence of theophylline and added roflumilast. The registry record does not report numerical results for those primary measurements, so the size and precision of any observed change cannot be described.
3. Trial Design
The registry classifies this study as Phase 3 and describes its model as single-group. Allocation is recorded as NA, and masking is recorded as none. The listed intervention sequence is theophylline for one week, followed by adding roflumilast for a further one week. Measurements are specified at baseline, Week 1 and 2. This is a repeated-measure sequence within a group, not a randomized comparison between treatment arms.
The brief summary calls the study a pilot and says it was designed to evaluate the effects of the two drugs on circulating HDAC levels, as well as corticosteroid effects on the beta-agonist bronchodilator response. It describes measurements after theophylline and again after roflumilast is added, including an acute effect of oral prednisone. The registered primary outcome is titled Bronchodilation and describes change in FEV1 and FVC. Change in HDAC2 Levels is listed as a secondary outcome.
The registry records enrollment of 13, whereas the brief summary says studies will be performed in 10 subjects. The record does not explain this difference or identify how many participants contributed data at each measurement occasion. The sponsor is UConn Health. The study start is recorded as 2014-12, primary completion as 2016-08, and status as completed.
Because no separate control group is described, changes across the measurement occasions cannot isolate treatment effects from other influences that may change over time. The sequential design also means that the later period includes the earlier treatment: roflumilast is added to theophylline rather than given as a standalone comparator. Details such as treatment adherence, washout procedures, the timing of each measurement beyond the listed occasions, and the 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.
Before assignment: Two of the 13 enrolled patients were found to be ineligible after being enrolled and therefore never started the study.
Overall Study
| Stage | Theophylline and Roflumilast |
|---|---|
| STARTED | 11 |
| COMPLETED | 8 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Theophylline and Roflumilast |
|---|---|
| Lost to Follow-up | 1 |
| Patient did not take drug as specified | 1 |
| Withdrawal by Subject | 1 |
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: Three patients did not complete the study and therefore their data was removed from the analyses.
| Characteristic | Unit | Theophylline and Roflumilast |
|---|---|---|
| Participants analysed | 8 | |
| Age, Continuous | years | 67.4 (SD 8.2) |
| Sex: Female, Male: Female | Participants | 4 |
| Sex: Female, Male: Male | Participants | 4 |
| Race/Ethnicity, Customized: White Non-Hispanic/Latino | Participants | 7 |
| Race/Ethnicity, Customized: African American | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Bronchodilation, measured over Baseline, Week 1 and 2.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | liters |
| Endpoint classification | Continuous Endpoint |
The primary outcome is titled Bronchodilation and is described as change in FEV1 L and FVC L, with measurements at baseline, Week 1 and 2. The registry specifies a mean as the summary parameter and standard deviation as the dispersion measure. FEV1 is the volume of air forcibly exhaled in the first second of a breathing test; FVC is the total volume forcibly exhaled during the test. These lung-function measures can describe airway limitation and the volume of air exhaled.
In general, reporting a mean gives a summary of the measured values in a group, while the standard deviation describes how spread out individual measurements are around that mean. They answer different questions: the mean describes the group’s average measurement, while the standard deviation conveys variation among observations. Neither alone establishes how precisely a treatment-related change has been estimated.
The registry outcome description identifies changes in FEV1 and FVC, but the numerical primary outcome results are not reported in the registry record. The record therefore does not allow readers to assess the direction, magnitude, or precision of the reported endpoint. The brief summary’s interest in corticosteroid effects on the bronchodilator response gives context for the study question, but does not replace numerical results for the registered lung-function outcome.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes an exploratory question: whether lung-function measurements and circulating HDAC levels change during a sequence in which participants receive theophylline and then receive roflumilast added to theophylline. It also describes interest in the acute effect of oral prednisone on the bronchodilator response to an inhaled beta agonist. The design can describe measurements over time in the studied group, but the registry record does not report the numerical outcome estimates needed to characterize those changes.
In particular, the primary outcome is described as change in FEV1 and FVC in liters at baseline, Week 1 and 2. No means, standard deviations, contrasts, confidence intervals, or p-values for these primary measurements are reported in the registry record. Consequently, the direction and size of any change, and the uncertainty around it, cannot be evaluated from the information recorded. The secondary outcome is Change in HDAC2 Levels, but its numerical results are also not reported in the registry record.
The single-group sequence limits causal interpretation even if measurements differ across time. A before-and-after difference may reflect the treatment sequence, but it may also reflect other changes occurring over time, measurement variability, or influences not documented in the record. The later measurements follow exposure to theophylline and addition of roflumilast; they do not compare the two drugs as independent alternatives. With no separate control group, the registry cannot establish what would have happened over the same period without the sequence or under another treatment.
The registry describes a study intended to provide preliminary data. That framing is consistent with treating the design as exploratory rather than as a definitive estimate of comparative treatment effects. However, the record does not report a protocol-level sample-size justification, analysis plan, or participant flow that would clarify the intended precision or how incomplete observations were handled. Enrollment is recorded as 13, while the brief summary refers to 10 subjects; the relationship between these figures is not explained.
The serious adverse event record lists 0 affected among 11 at risk in the Theophylline and Roflumilast group, and deaths are recorded as 0. These are counts for the registry’s safety reporting, not evidence that all possible harms were excluded. They should be read alongside the limited information about the number contributing safety data and the absence of additional event details. Overall, the registry record gives design and outcome definitions but does not provide the numerical efficacy results needed to judge observed changes or their precision.
9. Statistical Methods Explained
The study is registered as a single-group design, so its core data structure is repeated measurements from one treatment sequence rather than outcomes compared across independently assigned groups. The listed schedule is baseline, Week 1 and 2. Participants receive theophylline for 1 week, followed by roflumilast added for a further 1 week. This sequence can show how measurements vary across occasions, but it does not by itself separate treatment-associated change from change over time.
What does a mean and standard deviation describe?
The registry identifies the primary outcome summary as a mean and its dispersion as a standard deviation. In general, the mean describes the average measured value in a group. The standard deviation describes the spread of individual values around that average. A group mean can conceal variation among participants, so the dispersion statistic adds useful context about how consistent or variable the measurements are.
These descriptive statistics do not automatically quantify the precision of a treatment effect. Precision for a mean or contrast is commonly conveyed with a confidence interval, which in general represents a range of values compatible with the data and the statistical model at a stated confidence level. The numerical confidence intervals for the primary outcome are not reported in the registry record. Nor are the numerical means and standard deviations needed to assess the outcome directly.
Why is a single-group sequence different from a controlled comparison?
When a group is measured repeatedly, each measurement can be compared descriptively with earlier measurements. But without a separate control group, a difference cannot be attributed uniquely to the treatment sequence. The record does not describe random allocation to another treatment or to an untreated comparator. It also does not describe masking. Knowledge of treatment and measurement occasion can matter in general when outcomes involve participant effort or assessment, although the registry does not describe the measurement procedures in enough detail to assess that issue.
The sequence also constrains which contrast can be interpreted. Roflumilast is added after theophylline, so the later period combines the prior theophylline exposure with the added drug. It does not directly compare theophylline alone with roflumilast alone. The registry record does not report washout procedures or other design details that would clarify how carryover or period effects were considered.
How should planning calculations be read?
The registry’s sample-size assumptions describe a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. Such calculations are hypothetical planning exercises, not observed power and not evidence that the actual single-group study had the illustrated design. In particular, equal allocation between two arms does not match the registered single-group model. Any planning figures should therefore be interpreted as illustrations of assumptions, not as the trial’s enrollment target, achieved power, or evidence of efficacy.
In general, a sample-size calculation depends on assumptions about the effect to detect, variability, significance threshold, allocation, and analysis. Changing those assumptions changes the planning requirement. A calculation based on an observed effect can also be optimistic when the observed effect is uncertain. The registry record does not report the original protocol’s sample-size justification, so the planning illustration should not be treated as the design rationale.
What statistical results are missing from the registry record?
The numerical primary outcome results are not reported in the registry record. The record does not provide outcome estimates, confidence intervals, or test results that would show the amount of change and its uncertainty. It lists Change in HDAC2 Levels as a secondary outcome but likewise does not provide a numerical result for that endpoint. The analysis methods used to produce the outcome estimates, including any adjustment for baseline values or repeated measurements, are not reported in the registry record.
These omissions matter because a descriptive difference, a modeled treatment effect, and a statistical test are not interchangeable. A model can account for the correlation between repeated observations, while a simple comparison may not. The appropriate approach depends on the data structure and analysis plan. Without the plan and results, it is not possible to determine which approach was used or whether assumptions were checked.
In general, continuous outcomes can show greater variability than a simple normal model anticipates. When data are more dispersed than the model assumes, standard errors and confidence intervals may be too small if that extra variability is ignored. The registry record does not report a dispersion assessment, model diagnostics, or methods for handling outliers. This is a general statistical consideration, not a claim about the study’s actual data.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary outcome of Bronchodilation, described through change in FEV1 and FVC, and a secondary outcome of Change in HDAC2 Levels. The primary outcome has measurement occasions at baseline, Week 1 and 2. The brief summary also describes interest in the effect of oral prednisone on the response to an inhaled beta agonist. Considering multiple outcomes, measurement occasions, or contrasts can create a multiplicity issue: when many statistical questions are tested, the chance of at least one apparently notable result can increase. This is a general statistical concern, not evidence that any particular result is misleading.
Whether multiplicity was addressed, which outcome or contrast was designated as primary for inference, and whether any adjustment was planned are not reported in the registry record. The record also does not report a prespecified hierarchy of outcomes or a statistical analysis plan. Without those details, the strength of any hypothetical result across several outcomes or occasions could not be interpreted from the registry alone.
Missing-data handling and analysis populations are also not reported in the registry record. The record does not state how many participants had usable measurements at each occasion, how incomplete outcome data were handled, or whether analyses included all enrolled participants or a subset. Enrollment is recorded as 13, while the brief summary refers to 10 subjects; the record does not explain the difference. Those details matter because changing the set of participants contributing data can affect estimates, and missingness can introduce bias when it is related to participants’ outcomes or treatment experience.
These are reporting gaps, not proof that the study lacked procedures for multiplicity or missing data. The registry record does not establish what was done beyond what it reports.
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 |
|---|---|---|---|
| Theophylline and Roflumilast | 0 | 11 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Theophylline and Roflumilast | 0 of 11 |
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 |
|---|---|
| Theophylline and Roflumilast | 0 of 11 |
The listed safety group is titled Theophylline and Roflumilast. The registry records 11 at risk for serious adverse events and 0 affected; deaths are recorded as 0. The other adverse-event counts also list 11 at risk and 0 affected. These figures describe the safety information entered in the registry for that group.
A count of 0 serious adverse events among 11 at risk means that no serious adverse events are recorded as affecting participants in this entry. It does not establish that no adverse effects of any kind occurred, that every possible harm was assessed, or that the treatments are free of risk. The record does not provide serious adverse event terms, and it does not report detailed definitions, surveillance procedures, event timing, or the relationship of each event to treatment.
The safety denominator is not the same as the recorded enrollment: enrollment is 13, whereas the safety entry lists 11 at risk. The registry record does not explain the difference or state whether all participants had the same duration of safety follow-up. The counts should therefore be understood as registry-reported event summaries, not as a complete characterization of safety.
12. What the Result Does, and Does Not, Mean
The registry record identifies a small, single-group sequence in people with COPD, with theophylline followed by roflumilast added to the existing treatment. Its primary outcome is change in FEV1 and FVC in liters measured at baseline, Week 1 and 2. The study description also identifies circulating HDAC levels and the corticosteroid-related bronchodilator response as areas of interest.
What the record does not establish is the observed size or direction of changes in those outcomes. Numerical primary and secondary outcome results are not reported in the registry record. Without estimates and measures of precision, readers cannot determine whether the measurements changed, how large any change was, or how uncertain it may be. No conclusion about treatment effectiveness follows from the design description alone.
Even if numerical within-group changes were available, the single-group design would not provide a direct controlled estimate of what the same participants would have experienced under an alternative sequence or without treatment. The sequence compares different times and exposures, not independently assigned groups. The later period includes prior theophylline exposure as well as added roflumilast, which limits attribution of any change to one component.
The serious adverse event entry records 0 affected among 11 at risk and 0 deaths. Those counts are useful as a record of reported events, but they do not rule out other adverse effects or establish comprehensive safety. The registry does not give detailed safety procedures or explain why the safety group size differs from recorded enrollment.
The study may be read as a registry-described pilot investigation of biological and lung-function measures. Its record offers context about the intervention sequence and intended outcomes, but the absence of numerical outcome results and key analysis details limits the conclusions that can be drawn. The findings cannot be generalized beyond what the record documents, and the registry alone does not support a claim of benefit, lack of benefit, or comparative advantage.
13. Why This Trial Matters Statistically
This study is statistically instructive because its design and its stated questions must be kept distinct from a controlled treatment comparison. Repeated measurements can be informative about how outcomes vary during a treatment sequence. They do not, by themselves, show what would have happened over the same period under a different treatment or no treatment. That distinction is central when interpreting studies without a separate comparator.
The treatment order also matters. Roflumilast is added after the theophylline period, so measurements at the later occasion reflect a different stage of the sequence, not an isolated roflumilast group. This makes careful description of the estimand—the precise effect a study is trying to estimate—important in general. The registry record does not report a formal estimand or analysis plan.
The outcome structure highlights the difference between an endpoint definition and an endpoint result. The record names FEV1 and FVC changes and specifies mean and standard deviation, but it does not report the numerical results. A clear endpoint definition helps readers understand what was intended to be measured; it cannot substitute for effect estimates and uncertainty.
The entry also illustrates why safety denominators and enrollment should be read separately. Enrollment is recorded as 13, while the safety group lists 11 at risk. Without an explanation of participant flow or follow-up, those counts should not be treated as interchangeable.
Finally, a planning calculation based on an observed effect is not the same as evidence from a trial’s actual design. The stated illustration assumes two arms and equal allocation, whereas this study is registered as single-group. Recognizing that mismatch prevents hypothetical sample-size values from being mistaken for observed power or a description of how the trial was conducted.
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 main limitation for interpreting this study is its single-group structure. There is no separate control group in the registry description, and allocation is recorded as NA. Changes across baseline, Week 1 and 2 therefore cannot separate treatment-associated change from time-related change or other influences. The treatment sequence also means that the later period follows theophylline exposure and includes added roflumilast, rather than providing an independent comparison of the drugs.
The registry does not report numerical results for the primary outcome or the secondary HDAC2 outcome. It consequently does not permit assessment of effect size, direction, or precision. The statistical analysis methods, confidence intervals, test results, and handling of repeated measurements are not reported in the registry record.
Details needed to assess the study population and completeness of the evidence are also absent. The record gives enrollment of 13, while the brief summary says the study will be performed in 10 subjects. It does not explain the difference, describe participant flow, or identify how many participants contributed measurements at each occasion. Missing-data procedures and analysis populations are not reported in the registry record.
The brief summary calls the study a pilot, while the registry classifies it as Phase 3. The registry does not explain the relationship between those descriptions. It also does not report the protocol-level sample-size justification, multiplicity procedures, or a full statistical plan. The planning assumptions describe a two-arm illustration, which does not match the registered single-group design; they should not be taken as a description of the trial’s actual analysis.
Safety reporting is limited to the listed counts, with no serious adverse event terms and no detailed reporting procedures. These limitations restrict interpretation of both efficacy and safety from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Enhancement of Corticosteroid Efficacy in COPD — NCT02340520.
- Registry record last updated 2018-06-19; status last verified 2018-05.
- Results first posted 2018-06-19.
- 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.
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18. Record Summary
NCT02340520 is a completed study sponsored by UConn Health and registered as Phase 3. It concerns COPD and is classified as single-group, with allocation recorded as NA and masking as none. The registry records enrollment of 13; the brief summary describes a pilot planned for 10 subjects.
The intervention sequence is theophylline for 1 week, followed by roflumilast added for a further 1 week. The primary outcome, Bronchodilation, describes change in FEV1 and FVC in liters at baseline, Week 1 and 2, summarized by mean and standard deviation. Change in HDAC2 Levels is listed as a secondary outcome.
Numerical outcome results and important analysis details are not reported in the registry record. The safety entry lists 0 serious adverse events among 11 at risk and 0 deaths. The single-group sequence does not provide a like-for-like control comparison, and the registry record does not establish a causal treatment effect.