Reducing Diagnostic Error to Improve Patient Safety in COPD and Asthma (REDEFINE Study): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Reducing Diagnostic Error to Improve Patient Safety in COPD and Asthma (REDEFINE Study) (NCT03137303), a randomized phase 3 study. The primary outcome is Total Number of Healthcare Visits.

2. Clinical Question

The study’s stated purpose was to evaluate spirometry in identifying diagnostic error in patients with COPD and asthma. The outcome listing makes healthcare visits the primary endpoint, while a secondary outcome concerns the number of participants whose COPD and/or asthma diagnosis was consistent with spirometry results. These are related but distinct questions: the primary endpoint concerns healthcare use, whereas the secondary outcome concerns diagnostic consistency. The registry record does not report a numerical result for either outcome, so it does not establish the direction or size of any difference between groups.

3. Trial Design

The REDEFINE Study (NCT03137303) is listed as a Phase 3 randomized, parallel-group trial with no masking. The University of Illinois Chicago is named as sponsor. The study status is completed; the registry gives a start date of 2017-07-01, a primary completion date of 2019-09-30, and enrollment of 402. These record details describe the trial’s design and administrative status, not its clinical findings.

Randomized allocation means that assignment to study groups is intended to use chance rather than a clinician’s choice. In general, randomization can reduce systematic differences between groups at the point of assignment. It does not guarantee that groups will be identical, and it does not resolve issues such as missing outcome data or unclear outcome definitions. The registry does not report the allocation ratio or the sequence-generation and concealment procedures.

The parallel model means that participants were assigned to a group rather than described as switching between study conditions. The registry identifies Patient Subject Usual Care and Patient-Subject Intervention. It gives only partial arm descriptions: the usual-care description begins with information collection and medication-history details, while the intervention description begins with collection of demographic and comorbidity information. The descriptions are incomplete in the record, so they do not establish the full care pathway or the precise distinction between groups.

The intervention list includes spirometry at an initial visit, albuterol, and spirometry at 12-month follow-up. The registry does not explain how albuterol relates to the assigned intervention, or whether and how the listed procedures applied across the groups. The absence of masking is recorded, but the record does not explain whether outcome assessors or analysts were masked. A sample-size justification and detailed 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.

T0: Time of Enrollment - Baseline Visit

T1: 3-month Follow-up

Reasons for not completing this period:

T2: 6-month Follow-up

Reasons for not completing this period:

T3: 9-month Follow-up

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention to treat. Once randomized, patients were included in the analysis.

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: Intention to treat. Once randomized, patients were included in the analysis.

6. Primary Endpoint

The registry lists the primary outcome as Total Number of Healthcare Visits, measured over 1 year.

The primary endpoint is titled Total Number of Healthcare Visits, with a timeframe of 1 year. Its description says the study was to determine differences between groups in healthcare visits, including all-cause and respiratory-related acute care outpatient visits, emergency department visits, and hospitalizations. These categories cover several kinds of healthcare use, rather than a single narrowly defined event.

The registry labels the unit as participants and the parameter as a count of participants. That label does not by itself clarify whether the endpoint represents the number of visits, the number of participants with visits, or a particular summary combining visit categories. The operational definition, rules for counting repeat visits, and handling of participants with multiple types of visits are not reported in the registry record. This distinction matters because analyses and interpretations differ depending on whether the outcome is a count of events or a count of people experiencing an event.

In general, healthcare-use outcomes can describe how often services are used and can capture events across several care settings. A clearly defined endpoint is needed to know exactly what a group difference means. Since the registry record does not report outcome values or a detailed counting rule, it is not possible to determine the observed healthcare-use pattern or the precise interpretation of a potential difference from this record alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods connect the study question to a defined outcome, an analysis population, and an estimate of the difference between randomized groups. For REDEFINE, the record identifies randomization, a parallel-group design, a 1-year primary-outcome timeframe, and an intention-to-treat population. It does not report the outcome analysis, effect estimates, confidence intervals, p-values, or a detailed statistical plan. The concepts below are general explanations, not a description of methods confirmed to have been used in this trial.

What does randomization contribute?

General: Random assignment is intended to make treatment groups comparable at the point of assignment, including with respect to factors that may not have been measured. This supports a causal comparison when the groups are analyzed according to assignment and when outcome collection and follow-up are handled appropriately. Randomization does not ensure that all participants complete follow-up, prevent deviations from assigned care, or remove the need to define and analyze the outcome carefully. The registry does not report the allocation ratio or the detailed randomization procedures.

What kind of outcome is being analyzed?

The primary-outcome title refers to a total number of healthcare visits. The endpoint description includes several healthcare settings, while the unit and parameter are described in terms of participants. This leaves an important measurement question: is the analysis about events, such as repeated visits, or people who experienced an event? General: If each participant contributes a count of visits, the data are count-valued and the analysis must account for how event counts are distributed. If the outcome instead marks whether a participant had a visit, it is binary at the participant level. Those definitions are not interchangeable, and the registry does not report a detailed counting rule that resolves the distinction.

General: A model for event counts may be appropriate when the outcome is the number of events per participant, but the model must reflect the data’s distribution and the study design. Over-dispersion occurs when count variability is greater than a selected model expects; ignoring it can make uncertainty estimates too small. The presence or absence of over-dispersion in these data is not reported in the registry record. If the endpoint is instead whether a participant had an event, a method for binary outcomes may be considered. The registry does not identify which approach, if any, was used.

How should the group contrast be expressed?

General: A statistical analysis should define the contrast of interest and report an effect estimate on a scale suited to the outcome. For a count outcome, this could be expressed using a difference or a relative comparison, depending on the analysis plan; for a binary outcome, the effect scale should likewise be stated. These are general possibilities, not reported REDEFINE results. Without an endpoint definition and a posted estimate, no numerical or directional comparison can be interpreted.

A confidence interval communicates uncertainty around an estimate. It is not a guarantee that the true effect lies within the interval, and its interpretation depends on the analysis assumptions and study design. A p-value is a measure of how compatible the data are with a specified null model under those assumptions. Neither measure replaces the effect estimate or clarifies whether an outcome definition is meaningful. The registry does not report confidence intervals or p-values for the outcomes listed.

What is the role of the analysis population?

The registry states that the primary outcome population was intention to treat and that patients were included once randomized. General: An intention-to-treat approach compares participants according to their randomized assignment, preserving the comparison created by randomization. It is distinct from an analysis limited to participants who completed all procedures or followed the assigned care exactly. The record does not report whether such additional analyses were conducted, nor does it describe how participants with unavailable outcome information were handled.

What do planning assumptions tell us?

The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It also distinguishes participants per arm for non-time-to-event outcomes from total events for time-to-event outcomes. This illustration is not the trial’s own design justification and is not observed power. General: A planning calculation explores the sample size associated with stated assumptions; it does not establish that a trial had a particular probability of finding a result after the data were collected. The observed effect and the resulting planning values are not reported in the registry record used for this interpretation. The trial’s own sample-size justification is also not reported.

In general, a full statistical account would specify the endpoint precisely, the group contrast, the model, the handling of missing data, and any adjustments or sensitivity analyses. The registry record does not report those details. It therefore supports an explanation of the design and endpoint labels, but not a reconstruction of the analysis or a judgment about statistical precision.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and a secondary outcome, but it does not report a detailed multiplicity strategy. General: When a study evaluates multiple outcomes or multiple contrasts, the chance of at least one apparently unusual result can increase if each is assessed separately without a plan. A prespecified hierarchy or adjustment can address some multiplicity concerns, but whether either was used in REDEFINE is not reported in the registry record. No outcome-specific analysis results are reported, so the consequences of any multiplicity strategy cannot be assessed.

For missing data, the registry states that the primary outcome population was intention to treat and that patients were included once randomized. That statement describes the intended population, not the completeness of follow-up. The record does not report how many participants had unavailable outcome data, why data might be missing, or whether imputation or another missing-data method was used. General: Missing-data methods rely on assumptions about why values are unavailable. Those assumptions can affect estimates and uncertainty, so the amount and pattern of missingness are important to interpretation.

The registry does not report a detailed statistical analysis plan, sensitivity analyses, or a comparison of alternative analysis populations. It also reports no analyses in the outcome-analysis listing. As a result, the intention-to-treat statement cannot be taken as evidence that all randomized participants had complete data or that missingness was handled in a particular way. These omissions limit assessment of robustness and reproducibility from the registry record.

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 adverse-event record lists Patient Subject Usual Care with 231 participants at risk for serious events and 0 serious events; it lists Patient-Subject Intervention with 171 participants at risk and 0 serious events. The record also lists 0 other events in each group. Deaths are reported separately: 1 in Patient Subject Usual Care and 0 in Patient-Subject Intervention.

These are registry counts, not a comparison adjusted for follow-up time or participant characteristics. The record does not provide event descriptions, timing, exposure duration, or an assessment of whether a death was related to study participation. A death count should not be assumed to be included in the serious-event count, because the registry presents the figures separately and does not explain their relationship. The absence of reported serious events is not proof that no unreported event occurred, nor does it establish a comparative safety conclusion. The registry record does not report further safety analyses.

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

The record documents a randomized, parallel-group study intended to evaluate spirometry in relation to diagnostic error in COPD and asthma. It identifies healthcare visits over 1 year as the primary outcome and diagnostic consistency with spirometry as a secondary outcome. It also identifies the study as completed and records an enrollment of 402. These details describe what the study was set up to examine, not what its results were.

The outcome results are not reported in the registry record. Consequently, it is not possible from this record to say whether healthcare visits differed between groups, whether diagnostic consistency differed, or how large and precise any difference may have been. The record does not supply an estimate, confidence interval, or inferential analysis for either outcome. A lack of posted numerical results should not be interpreted as evidence of no effect or as evidence of benefit.

The primary endpoint’s wording also leaves uncertainty about whether the intended analysis counted visits or participants with visits. That distinction affects what a group comparison would mean. The arm descriptions are incomplete, and the registry does not explain how the listed spirometry procedures and albuterol relate to the assigned groups. These limitations prevent a detailed reconstruction of the intervention contrast.

General: Randomization can support a fair comparison, but interpreting that comparison requires clear outcome definitions, complete reporting, and an account of uncertainty and missing data. Those elements are not available in the registry record for the primary outcome. The safety figures are descriptive counts and do not by themselves establish a treatment-related safety difference. The most defensible conclusion is therefore about the study’s design and the limits of the posted information, not about the effect of the intervention.

13. Why This Trial Matters Statistically

This trial is statistically notable because its stated purpose concerns diagnostic error, while its primary endpoint concerns healthcare use. These outcomes address different dimensions of the study question. Diagnostic consistency with spirometry speaks to agreement between diagnosis and test results; healthcare visits describe utilization across several care settings. A clear account of how those outcomes were defined and how they relate to the study objective is important for interpreting any result.

The primary-outcome labels also illustrate why an endpoint must be operationally precise. The title refers to a total number of visits, but the unit and parameter refer to participants. If the underlying data represent repeated events, the statistical analysis must account for event counts; if they represent people with an event, the analysis answers a different question. The registry does not resolve this distinction. This is not merely a technical detail: the endpoint definition determines the estimand, or the exact quantity the study is trying to compare.

The randomized design and intention-to-treat statement provide useful information about the intended comparison. Yet statistical interpretation also depends on outcome reporting, missing-data handling, and a transparent analysis plan. Those details and the numerical results are not reported in the registry record. The trial therefore demonstrates a broader reporting principle: design information alone cannot establish an effect, and an endpoint title alone cannot identify the exact analysis.

For researchers and readers, the record is a reminder to distinguish planned questions from observed findings. It gives the study’s purpose, groups, timeframe, and selected outcomes, but it does not report the results needed to assess the size or precision of a difference. Keeping that distinction clear prevents design features or descriptive safety counts from being mistaken for evidence about efficacy or comparative safety.

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.

Interpretation is limited because numerical results for the primary and secondary outcomes are not reported in the registry record. There are no posted group outcome values, effect estimates, confidence intervals, or p-values from which to assess direction, magnitude, or precision. The registry’s analysis listing reports no analyses.

The primary endpoint is not fully specified in the record. Its title refers to a total number of healthcare visits, while its unit and parameter are expressed in terms of participants. The description includes several types of care, but does not report how repeat visits, overlapping categories, or the final summary measure were handled. This leaves uncertainty about what the intended comparison represents.

The descriptions of both study arms are incomplete. The record lists spirometry at an initial visit, albuterol, and spirometry at 12-month follow-up, but does not fully explain how those interventions were assigned or how the arms differed in delivered care. The allocation ratio and detailed randomization procedures are not reported. Masking is listed as none, but the record does not clarify whether assessors or analysts were masked.

The registry does not report a detailed statistical analysis plan, sample-size justification, missing-data methods, multiplicity approach, or sensitivity analyses. Although the primary population is described as intention to treat, completeness of follow-up and handling of unavailable outcomes are not reported. The safety counts are also limited by the absence of event descriptions and exposure details. These gaps mean that the registry record supports a description of the trial setup, but not a complete evaluation of its results or analytical robustness.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Reducing Diagnostic Error to Improve Patient Safety in COPD and Asthma (REDEFINE Study) — NCT03137303.
• Registry record last updated 2024-02-26; status last verified 2024-02.
• Results first posted 2021-07-22.
• 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

NCT03137303, the REDEFINE Study, is listed as a completed Phase 3 randomized, parallel-group trial with no masking. The University of Illinois Chicago is named as sponsor. The record gives enrollment of 402, a start date of 2017-07-01, and a primary completion date of 2019-09-30.

The stated purpose was to evaluate spirometry in identifying diagnostic error in COPD and asthma. The primary outcome was Total Number of Healthcare Visits over 1 year; the secondary outcome concerned diagnosis consistency with spirometry results. The primary analysis population is described as intention to treat, with patients included once randomized. Numerical outcome results and statistical analyses are not reported in the registry record. The record lists 0 serious adverse events in both groups and deaths of 1 in usual care and 0 in the intervention group.