Mid-Q Response Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mid-Q Response Study (NCT04180696), a randomized na study. The primary outcome is Clinical Composite Score.

2. Clinical Question

This is a comparison of two device-programming strategies among people receiving CRT, not a comparison of CRT with no CRT. The planned contrast asks whether the adaptive algorithm is associated with a more favorable clinical status classification than standard, nonadaptive programming. The score also includes an Unchanged category and a Worsened category, so the primary measure is not simply a count of deaths or hospitalizations.

The study was described as prospective, multicenter, randomized, controlled, single-blinded and post-market. Its stated setting was approximately 60 centers in Asia. The record gives enrollment as 177 and describes random assignment in a 1:1 ratio. It does not report comparative results for the primary question, so the direction and precision of any difference between groups cannot be assessed from the record details available.

3. Trial Design

Mid-Q Response was a randomized, parallel-group, single-blinded, post-market interventional study. The registry lists its status as completed and its phase as NA. The start date is 2020-01-23, and the primary completion date is 2024-03-28. Enrollment is recorded as 177. The sponsor is Medtronic Cardiac Rhythm and Heart Failure.

Participants were randomly assigned to aCRT ON or aCRT OFF. The study description states a 1:1 assignment ratio. In the ON group, AdaptivCRT was programmed to use the adaptive algorithm; in the OFF group, it was programmed as nonadaptive CRT, described as standard CRT. Control-group optimization was left to physician discretion, with the method of AV and VV optimization to be collected. The record does not report additional details about the randomization sequence, concealment, or how the single-blind arrangement was maintained.

The primary outcome was assessed at 6 months post-randomization in all randomized subjects. It was the Clinical Composite Score, which categorizes clinical status as Improved, Unchanged or Worsened. Secondary outcomes listed in the record include change in NYHA class, hospitalizations for worsening heart failure, all-cause mortality and cardiovascular-related mortality. The registry record does not report the detailed statistical analysis plan, including the exact method for comparing the primary categories.

Randomization can help balance measured and unmeasured characteristics across groups on average, but it does not guarantee that the groups are identical. A parallel-group design compares the assigned strategies across groups rather than having each participant receive both strategies. Interpretation still depends on how outcomes were collected, how participants were analyzed, and how missing outcomes and departures from assigned treatment were handled. Those details are not reported in the registry record beyond the endpoint’s stated classification rules.

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: Patients were enrolled as long as they met the inclusion criteria and were willing to consent. A total of 177 subjects were enrolled, of which 171 subjects were randomized between Adaptive and Conventional CRT.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized subjects

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: Number of subjects randomized following successful implant

6. Primary Endpoint

The registry lists the primary outcome as Clinical Composite Score, measured over 6 months post-randomization.

The primary endpoint is the Clinical Composite Score at 6 months post-randomization. It classifies each patient as Improved, Unchanged or Worsened. A patient is classified as Worsened in the event of death, hospitalization for worsening heart failure, worsening NYHA class using last observation carried forward, or worsening on the Global Assessment Score. Exiting the study or crossing over because of worsening heart failure also leads to a Worsened classification.

A patient is classified as Improved if the patient is not Worsened and has improvement in NYHA class or Global Assessment Score. Patients who meet neither definition are Unchanged. This category also includes patients missing NYHA class and Global Assessment Score data when they are not classified as Worsened because of death, heart-failure hospitalization, exit or crossover.

A composite endpoint can capture several clinically relevant ways a patient’s status may change, rather than focusing on a single event. It can also make the result depend on the definitions and hierarchy used to assign categories. In this endpoint, Worsened events take precedence over improvement, while Unchanged includes some participants with missing status measures. The registry record does not report the number in each category or a between-group estimate, so the primary outcome’s observed distribution and comparative precision cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization assigns participants to study groups by chance. In general, this reduces systematic differences in prognosis between groups and supports a causal interpretation of the assigned-strategy contrast, provided the trial is analyzed and followed appropriately. Randomization does not guarantee identical groups, remove chance variation, or resolve problems caused by missing outcomes or departures from assigned treatment. The record describes random assignment in a 1:1 ratio but does not report the sequence-generation or concealment methods.

What does the three-category endpoint represent?

The Clinical Composite Score places participants into Improved, Unchanged or Worsened categories at 6 months post-randomization. These categories are defined using clinical events and status measures. Death, worsening-heart-failure hospitalization, worsening NYHA class, worsening Global Assessment Score, and certain exits or crossovers lead to a Worsened classification. Improvement in NYHA class or Global Assessment Score leads to Improved only when the participant is not Worsened. Other participants are Unchanged, including some with missing status data.

This structure is important for analysis. A three-category endpoint contains more information than a yes-or-no outcome if the categories are retained, but an analysis may also choose a particular contrast, such as the proportion Improved. Different contrasts answer different questions. Comparing the full category distribution asks whether the overall pattern differs between groups; comparing only improvement asks about one category against its complement. The registry record does not report the exact primary comparison method or whether the full distribution or a particular contrast was analyzed.

How should uncertainty be understood?

In general, an estimate is the observed summary of a contrast in the study data, while a confidence interval communicates uncertainty around that estimate under the analysis assumptions. A narrow interval indicates greater precision than a wide interval, but precision is not the same as clinical importance. A p-value summarizes how unusual data at least as incompatible with a specified null hypothesis would be under that hypothesis and model. It does not give the probability that the null hypothesis is true, nor does it measure the size or value of an effect.

The registry record does not report a primary effect estimate, confidence interval or p-value. It is therefore not possible to discuss the precision or statistical evidence for the primary comparison. The absence of those statistics in the registry record is not evidence that there was no effect; it means the comparative result cannot be characterized from the reported details.

Why does analysis population matter?

The primary endpoint description names all randomized subjects as the population. In general, analyzing participants according to their randomized assignment preserves the comparison created by randomization, even if treatment was not received exactly as assigned. Other analysis populations may be defined for different purposes, but their membership and rationale need to be specified. The registry record does not report additional analysis populations or explain how treatment discontinuation, protocol deviations or other departures were handled.

Endpoint rules also affect how missing observations are treated. The score specifies that missing NYHA class and Global Assessment Score data result in Unchanged when the participant is not already classified as Worsened under the listed event rules. This is a classification rule, not a report of how many outcomes were missing. The record does not provide the amount or pattern of missing data, or sensitivity analyses that might test whether assumptions about missing status affect conclusions.

What does the planning illustration mean?

The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between the groups and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. In general, a planning calculation estimates the sample size needed to target a chosen level of statistical power under its assumptions. It is not an observed result and is not observed power. A planning value also does not show that the trial’s actual design was based on that calculation.

The record does not report a sample-size justification or the trial’s own statistical plan. The registry entries available do not include a numerical planning output or a reported observed effect for the primary endpoint. In addition, the endpoint has several categories, and the registry record does not reduce it to a single comparison. A planning calculation based on an observed effect should therefore be read as an illustration, not as proof that the study was designed around that effect or that its primary analysis followed those assumptions.

Why can over-dispersion matter?

In general, count outcomes can vary more than a simple statistical model expects. This is called over-dispersion, and ignoring it can make uncertainty look smaller than it is. A suitable model or robust uncertainty estimate can account for extra variation. The primary Clinical Composite Score is reported as a count of participants assigned to categories, not as a repeated-event rate. The registry record does not identify a model for the primary endpoint, so there is no basis to say that an over-dispersion adjustment was used or required for its analysis.

Secondary outcomes include hospitalization and mortality measures, but their detailed definitions, analysis models, estimates and uncertainty are not reported in the registry record. No specific inferential procedure should be attributed to the trial without those details.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary Clinical Composite Score and secondary outcomes that include change in NYHA class, hospitalization for worsening heart failure, all-cause mortality and cardiovascular-related mortality. It does not report a multiplicity strategy. In general, testing several outcomes or contrasts can increase the chance of at least one apparently notable result arising by chance. Prespecified priorities, adjusted thresholds or a hierarchical testing plan can address this issue, but the registry record does not state whether any such approach was used.

The endpoint itself has three categories, and the registry’s description gives rules for classifying participants. It does not report the exact statistical contrast used for the primary analysis. A comparison of improvement alone and a comparison of the entire category distribution would answer different questions; the analysis plan is not reported in the registry record.

The primary outcome population is described as all randomized subjects. The record does not report additional analysis populations, how participants were handled if they did not follow assigned programming, or whether the analysis retained participants in their randomized groups. These details matter because exclusions after randomization can weaken the comparability created by random assignment.

The classification rules assign some participants with missing NYHA and Global Assessment Score data to Unchanged, unless they meet a Worsened criterion. The number of participants with missing measurements, the reasons for missingness, and any sensitivity analyses are not reported in the registry record. In general, missing-data assumptions can influence a result when the likelihood of missingness is related to a participant’s health status. The stated category rule clarifies part of the endpoint definition but does not reveal how often it was applied or how robust a comparison would be to alternative assumptions.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac failure (8.2%), lead dislodgement (3.5%), ventricular tachycardia (2.4%), covid-19 (2.4%), pneumonia (2.4%).

The adverse-event record lists serious adverse events for 27 of 86 participants at risk in the aCRT ON group and 24 of 85 at risk in the aCRT OFF group. Other adverse events are listed for 8 of 86 and 14 of 85, respectively. Deaths are listed for 5 in the aCRT ON group and 6 in the aCRT OFF group. These are descriptive counts; the registry record does not report a comparative statistical analysis of these safety figures.

Counts alone do not show whether differences between groups are compatible with chance variation or how precisely any contrast is estimated. They also do not establish that an event was caused by the assigned programming. The registry record does not report event timing, severity breakdown beyond the serious-event grouping, exposure-adjusted rates, or a causal attribution analysis in the registry record.

Listed serious-event terms and percentages are cardiac failure, 8.2%; lead dislodgement, 3.5%; ventricular tachycardia, 2.4%; COVID-19, 2.4%; pneumonia, 2.4%; and atrial fibrillation, 2.3%. The registry record does not specify in this summary how these percentages are allocated by arm or their denominators. They should not be interpreted as comparative risks between the randomized groups.

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

The registry record establishes the study question and design: a randomized, parallel-group comparison of adaptive and nonadaptive CRT programming, with the primary endpoint defined as clinical status at 6 months post-randomization. The endpoint is a composite classification that assigns participants to Improved, Unchanged or Worsened using clinical events and status measures. The record also lists secondary outcomes and descriptive safety counts.

It does not report the primary outcome distribution by group, the estimated comparison, a confidence interval or a p-value. Thus, the registry entries do not establish whether the groups differed, in which direction they differed, or how precise any difference was. The study’s completed status and enrollment figure do not answer those outcome questions. Nor can safety counts alone establish a causal treatment effect or settle the primary comparison.

Even if an outcome estimate were available, its meaning would depend on the definition of the endpoint, the participants included in the analysis, the handling of missing status measures, and the uncertainty around the estimate. For this study, some missing NYHA and Global Assessment Score data can lead to an Unchanged classification when no listed worsening event applies. That rule is part of the endpoint definition; without information on the amount of missing data and the analysis results, its practical influence cannot be assessed.

The results would also need to be interpreted in the context of the population and intervention described: CRT-indicated patients with moderate QRS duration, preserved AV conduction and left bundle branch block, assigned to aCRT ON or aCRT OFF. The record describes approximately 60 centers in Asia, but does not report enough outcome or participant detail to establish how results might apply to other populations or settings.

The appropriate statistical conclusion from the available record is limited. The research question and endpoint are specified, and adverse-event counts are listed, but comparative primary-outcome estimates and their uncertainty are not reported in the registry record. This does not establish that the strategies are equivalent or that either is superior. It identifies a reporting gap that prevents a substantive assessment of the primary efficacy comparison.

13. Why This Trial Matters Statistically

This trial is statistically notable for using a randomized comparison of two programming strategies while defining its primary outcome as a multi-component clinical classification. The design can support a direct comparison of assigned strategies, but the interpretation depends on the exact contrast and the handling of the three outcome categories. Reporting the category counts and a clearly defined between-group estimate would make the primary question assessable.

The endpoint rules combine events and status measures with a hierarchy: listed worsening events take precedence, while improvement requires that a participant is not Worsened. The Unchanged category includes some participants who lack NYHA class and Global Assessment Score data. This makes transparent reporting of category assignment and missingness especially relevant. A label such as Improved alone would not reveal the full distribution or the components contributing to worsening.

The randomized design and stated all-randomized primary population are useful features for understanding the intended comparison. However, the record does not report the detailed analysis plan, the actual primary estimate, or uncertainty statistics. Without these, readers cannot assess the magnitude or precision of a between-group difference, evaluate the planned contrast, or judge how the endpoint distribution supports the stated objective.

The safety record also illustrates why descriptive counts and inferential comparisons should be kept distinct. Serious events, other events and deaths are listed by group, but no comparative analysis is reported in the registry record. Counts can identify what was recorded, but do not by themselves show whether group differences are precise or causally attributable to the programming strategy.

Finally, planning illustrations should remain separate from evidence observed in the study. The stated assumptions describe an illustrative calculation, not observed power and not necessarily the trial’s own design basis. Clear reporting of the design rationale, statistical plan, outcome estimates and uncertainty would allow readers to distinguish the intended question from the evidence available to answer it.

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 most important limitation for statistical interpretation is that the registry record does not report comparative results for the primary Clinical Composite Score. There are no group-specific category counts, estimated contrast, confidence interval or p-value in the registry record. The primary question therefore cannot be answered from this record.

The endpoint includes several components and three possible classifications. Although the registry gives detailed classification rules, it does not report how many participants were classified as Improved, Unchanged or Worsened, or how the different components contributed. The record also does not report the exact statistical contrast used for the primary analysis, so it is unclear whether the analysis focused on improvement or the full category distribution.

The record names all randomized subjects as the primary-outcome population, but does not report analysis details for treatment departures, withdrawals or other post-randomization events beyond endpoint rules for exit or crossover because of worsening heart failure. It describes a rule for some missing NYHA and Global Assessment Score data but does not report the extent or pattern of missingness, or sensitivity analyses.

The statistical analysis plan, sample-size justification, multiplicity strategy and interim-analysis approach are not reported in the registry record. The registry also does not report the randomization-sequence method, allocation concealment, or details of how single blinding was implemented. These omissions limit assessment of the planned analysis and safeguards against bias, without establishing that any particular method was or was not used.

The safety information is descriptive in the registry record. Comparative uncertainty, event timing, exposure-adjusted rates, and arm-specific detail for the listed serious-event terms are not reported in the registry record. The study description identifies an intended population and setting, but the registry entries do not provide enough outcome data to assess generalizability or the consistency of effects across participant subgroups.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Mid-Q Response Study — NCT04180696.
• Registry record last updated 2025-07-09; status last verified 2025-04.
• Results first posted 2025-05-30.
• 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

Mid-Q Response was a completed, randomized, parallel-group, single-blinded, post-market study sponsored by Medtronic Cardiac Rhythm and Heart Failure. Enrollment is recorded as 177. The study compared AdaptivCRT programmed ON, using the adaptive algorithm, with AdaptivCRT programmed OFF as nonadaptive standard CRT. It was described as taking place at approximately 60 centers in Asia.

The primary endpoint was the Clinical Composite Score at 6 months post-randomization, with Improved, Unchanged and Worsened classifications. The primary population was all randomized subjects. Secondary outcomes listed include change in NYHA class, hospitalization for worsening heart failure, all-cause mortality and cardiovascular-related mortality.

The record does not report comparative primary-outcome estimates or uncertainty statistics. It lists serious adverse events, other adverse events and deaths by group, but does not report comparative safety analyses in the registry record. The detailed statistical plan, multiplicity approach, sample-size justification and missing-data sensitivity analyses are not reported in the registry record.