Comparative Efficacy of Water & Indigo Carmine vs. Water or Air Method on Adenoma Detection Rate (ADR) - a Randomized Controlled Trial (RCT): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparative Efficacy of Water & Indigo Carmine vs. Water or Air Method on Adenoma Detection Rate (ADR) - a Randomized Controlled Trial (RCT) (NCT01607255), a randomized phase 4 study. The primary outcome is Number of Participants With Detected Proximal Diminutive (<10 mm) Adenoma Detection Rate.

2. Clinical Question

The trial addresses a procedural detection question, not a question about cancer incidence or mortality as a measured primary outcome. Its summary explains the rationale as a concern about lesions missed during screening colonoscopy, particularly in the proximal colon. That rationale motivates studying adenoma detection, but it does not establish that a difference in detection would translate into a difference in later cancer outcomes. The registry record describes the intended comparison and endpoint; it does not show whether the proposed detection benefit was observed.

3. Trial Design

The registry identifies NCT01607255 as a completed, randomized, single-masked, parallel-group Phase 4 trial sponsored by the VA Office of Research and Development. Enrollment is recorded as 480. The listed study start date is 2013-05-16, and the primary completion date is 2017-06-30. These administrative details describe the registration record and do not supply the endpoint findings.

The three listed procedures are water exchange, water exchange plus dye, and the air method. The water exchange descriptions state that residual air is suctioned, water is infused during advancement, and dirty water is suctioned and replaced with clean water; air is not insufflated until the cecum is reached. The dye arm specifies 0.008% indigocarmine in the infused water. The air arm describes gentle advancement with minimal air insufflation when necessary, with assistance or a change in patient position if needed to facilitate scope passage.

Random allocation is recorded, but the method used to generate the allocation sequence, conceal assignments, and maintain masking is not reported in the registry record. The registry labels masking as single but does not identify who was masked. It also does not report how the three procedures were allocated, whether allocation ratios were equal, or whether the same procedural staff performed each method.

The primary outcome is listed as a number of participants with detected proximal diminutive adenomas, with a timeframe of 36 months. The record does not explain how that timeframe relates to individual colonoscopy procedures or when outcome ascertainment occurred. It does not report the sample-size justification, protocol deviations, participant flow, or the number included in an endpoint analysis. The enrollment figure should therefore not be read as the analyzed denominator for the primary outcome. Results are not reported in the registry record, so the design description alone cannot establish comparative efficacy.

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.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Detected Proximal Diminutive (<10 mm) Adenoma Detection Rate, measured over 36 months.

The primary endpoint is titled as the number of participants with detected proximal diminutive adenoma detection rate. The description frames it as detection of proximal diminutive adenomas during screening colonoscopy using the air method, water exchange, or water exchange with dye. The title defines diminutive lesions as <10 mm, and the registered timeframe is 36 months. The record classifies the outcome as a binary count: participants with an event.

In general, an adenoma detection rate is used as a quality indicator because it represents whether adenomas were detected during colonoscopy in the population being assessed. A binary participant-level outcome distinguishes participants with a detected lesion from those without one under the outcome definition. To interpret a rate or compare rates, readers need the event counts and the relevant denominators for each arm, alongside a clear account of how lesions and participants were classified. Those primary-outcome counts, denominators, and comparisons are not reported in the registry record.

The focus on proximal diminutive adenomas makes the outcome narrower than detection of any adenoma or measurement of all colorectal neoplasms. The registry rationale discusses possible implications of missed lesions, but the recorded endpoint is detection during screening colonoscopy, not interval cancer, cancer mortality, or a direct measure of long-term clinical benefit. The registered description does not specify whether multiple qualifying lesions in a participant affect the endpoint, how location was defined, or how borderline lesion size was assessed. Those operational details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies randomization and a parallel-group design. In general, randomization is intended to make treatment groups comparable with respect to both measured and unmeasured characteristics, on average, so that outcome contrasts can be interpreted more credibly. It does not guarantee balance in a particular trial, and it cannot correct problems in outcome measurement or incomplete reporting. The record does not describe the allocation sequence, concealment procedures, or baseline characteristics, so those aspects of the design cannot be assessed.

What does a binary endpoint represent?

The primary outcome is classified as a binary count of participants with an event. In general, a binary endpoint records whether each participant meets a defined outcome criterion, rather than how many lesions that participant has or how long an event takes to occur. A group count is interpretable alongside its denominator. A rate comparison can then be expressed as an absolute difference or another effect measure, with uncertainty describing the range of values compatible with the data and analysis. The registry does not report the primary-outcome counts, denominators, effect estimates, or confidence intervals, so no such comparison can be interpreted for this trial.

The endpoint name refers to an adenoma detection rate, while the outcome classification describes a number of participants with detected adenomas. The distinction matters: an event count alone is not a rate unless its denominator is known. In general, investigators also need a prespecified definition of qualifying lesions and a consistent approach to applying it across arms. Details such as lesion location rules, size assessment, and handling of multiple lesions per participant are not reported in the registry record.

How should comparisons among procedures be approached?

With multiple intervention groups, analyses may compare each procedure with a selected reference group or may make several pairwise comparisons. In general, testing multiple contrasts can increase the chance of at least one false-positive result if no multiplicity strategy is used. A prespecified analysis plan can define the primary contrast, testing order, or adjustment method. The registry record does not report a primary contrast, a multiplicity adjustment, or an analysis plan. The entry that the outcome has several categories or time points and was not reduced to one comparison further limits interpretation of the posted results.

A p-value, when reported, addresses how compatible the data are with a specified null hypothesis under the assumptions of the statistical test. It does not state the probability that a treatment is effective, and it does not measure clinical importance. A confidence interval is generally useful because it shows the range of effect estimates reasonably compatible with the data and the analysis assumptions. Neither a p-value nor a confidence interval for the primary outcome is reported in the registry record. It is therefore not possible to evaluate statistical significance or precision from the recorded outcome information.

What do the planning assumptions mean?

The stated sample-size illustrations are planning calculations based on the observed effect, not a description of the trial's original design justification. The assumptions recorded for those illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. In general, such an illustration asks how many participants per arm would be needed under its chosen assumptions to detect a specified effect with a chosen power. It is not observed power, and it is not evidence that the trial had that planned sample size or analysis.

The record says that non-time-to-event illustrations give participants per arm, while time-to-event illustrations give total events. The primary endpoint is listed as a binary count, not a time-to-event outcome. The numerical sample-size justification for the trial and its intended power are not reported in the registry record. The registration also does not provide a basis for assessing whether the planning assumptions match the original protocol.

What can be inferred from the safety summaries?

For adverse events, the registry lists group-level participants at risk and affected. In general, an affected-participant count describes how many participants experienced an event under the registry's reporting definition; it is not necessarily the number of separate event episodes. Comparing groups requires consistent definitions, follow-up, and denominators. Serious-event categories and severity are distinct from the primary endpoint, and a count alone does not establish that a procedure caused an event. The record does not provide enough context to estimate comparative safety effects or assess the timing and relatedness of events.

The statistical methods used for the primary outcome, including any adjustment for covariates, handling of clustering or repeated observations, missing-data method, and confidence-interval procedure, are not reported in the registry record. No additional analysis should be inferred from the randomized design or from the sample-size illustration assumptions. Statistical interpretation is limited to the information actually recorded.

10. Multiplicity, Missing Data and Analysis Populations

The registry does not describe a statistical analysis plan for the primary endpoint. It lists no analyses and indicates that the primary outcome has several categories or time points and was not reduced to one comparison. The record does not identify a primary contrast among water exchange, water exchange plus dye, and air, nor does it state whether other comparisons were planned. It also does not report any method for controlling multiplicity. In general, multiple outcome contrasts or time points can complicate interpretation because repeated testing may increase the chance of a false-positive finding unless the analysis plan addresses that issue.

Missing-data procedures and analysis populations are not reported in the registry record. The record does not say how participants with incomplete colonoscopy, unavailable outcome assessment, withdrawal, or protocol deviations were handled. It does not identify an intention-to-treat, per-protocol, or other analysis population for the primary endpoint. These omissions prevent readers from assessing whether all randomized participants contributed to the reported analysis or whether exclusions could have affected the comparison. The enrollment figure does not establish the endpoint-analysis denominator.

The record also does not report outcome-adjudication procedures, blinding of outcome assessors, or rules for handling multiple lesions in a participant. Such details can matter for consistent classification of a detection endpoint. No assumptions about missingness, imputation, exclusions, or adjustment should be inferred in the absence of a registry description.

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

Serious events with the highest arm-level rate: post polypectomy abdominal pain (1.9%), post procedural bleeding (0.6%), cardiovascular event (0.6%).

The registry lists serious adverse events by procedural group. It records 4 affected participants among 161 at risk in the water exchange group, 3 among 160 at risk in the water exchange plus dye group, and 1 among 159 at risk in the air group. It records 0 other adverse events for each group and 0 deaths for each group. These are counts in the registry safety summary, not estimates of a causal effect.

The registry separately lists post polypectomy abdominal pain at 1.9%, post procedural bleeding at 0.6%, and cardiovascular event at 0.6% among the top serious-event terms. The record does not specify the denominator for these percentages or link each term to a particular group. They should not be treated as arm-specific percentages or combined with the group counts to derive additional rates.

In general, adverse-event counts need context: event definitions, reporting period, severity criteria, relatedness assessment, and completeness of follow-up all influence interpretation. The record does not provide that detail for these summaries. Serious events can occur during a study without being caused by the assigned procedure. The listed counts alone therefore do not establish comparative safety or explain the circumstances of any event.

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

The record establishes that investigators randomized participants among three colonoscopy approaches and defined a primary question about detecting proximal diminutive adenomas. It documents the intended clinical rationale and gives procedural descriptions for water exchange, water exchange with indigo carmine, and air. It also identifies the endpoint timeframe and reports summary serious adverse event counts. Those details describe the design and limited posted safety information.

The record does not show whether adding dye to water exchange increased, decreased, or left unchanged the number of participants with detected proximal diminutive adenomas relative to either comparator. It does not give the primary endpoint results, comparative effect estimates, uncertainty intervals, or an analysis plan. Accordingly, the trial cannot be interpreted as demonstrating superiority, equivalence, or lack of benefit on the basis of this registry record.

The registry's rationale discusses a possible relationship between improved detection and reducing the burden of post-screening interval cancers. That is a motivation for studying detection, not a finding from the registered primary endpoint. The endpoint described is adenoma detection during screening colonoscopy. The record does not report interval colorectal cancer outcomes, cancer mortality, or evidence that a difference in detection translated into a long-term outcome.

The safety summaries also have a limited meaning. They show reported serious adverse event counts and zero recorded deaths in the group listings, but do not establish the cause of events or a comparative safety effect. The entries for serious-event terms lack group-level attribution in the listed information. More complete outcome and methods reporting would be needed to assess efficacy, precision, safety, and the clinical importance of any contrast.

13. Why This Trial Matters Statistically

This trial is statistically relevant because it compares procedural approaches using a detection endpoint that is framed as a quality indicator for screening colonoscopy. Its randomized, parallel-group design is intended to support a fair comparison, while the three approaches make the definition of the primary contrast especially important. Readers need to know which comparison was primary and how other contrasts were handled to interpret the evidence without overemphasizing an isolated result.

The endpoint also illustrates the importance of connecting an outcome label to its analysis denominator. The registry names an adenoma detection rate but classifies the measure as a number of participants with an event. For a reader to interpret a rate, the number meeting the endpoint must be paired with the relevant group denominator and an explicit outcome definition. The record does not report these primary-outcome details.

The case further shows why an intervention rationale should be kept separate from observed evidence. The summary explains why investigators were interested in improving proximal lesion detection, and the procedural descriptions clarify the intended differences between approaches. Neither the rationale nor the design can substitute for posted comparative results. Here, the missing outcome estimates prevent conclusions about the magnitude, direction, and precision of any treatment contrast.

Finally, safety counts and planning assumptions answer different questions from the primary outcome. Serious adverse event summaries do not establish detection effects, and sample-size illustrations do not report observed power or validate the original trial design. Clear reporting of endpoint data, analysis populations, multiplicity handling, missing-data procedures, and uncertainty would be needed to make the statistical evidence fully interpretable.

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.

A central limitation of the registry record is the absence of primary endpoint results. It does not report arm-specific detection counts, denominators, effect estimates, confidence intervals, or test results. It also states that the endpoint was not reduced to one comparison because it has several categories or time points. The direction and precision of the primary comparison therefore cannot be assessed.

The population description is limited. The summary refers to sedated Veterans undergoing screening colonoscopy, and the condition is listed as colorectal neoplasms, but the record does not report detailed eligibility criteria or participant characteristics. It does not describe the method of randomization, allocation concealment, or who was masked despite the single-masked designation. Generalizability and possible baseline imbalance cannot be evaluated from the listed information.

The endpoint description does not explain operational details such as how proximal location was defined, how lesion size was determined, how detection was adjudicated, or how multiple lesions in one participant were handled. The timeframe is recorded as 36 months, but its relation to the timing of the colonoscopy assessment is not clarified. Missing-data handling, analysis populations, protocol deviations, multiplicity control, and the primary statistical model are also not reported in the registry record.

Safety interpretation is restricted by limited context about event definitions, timing, relatedness, and the denominator used for the serious-event term percentages. Group counts are reported, but the record does not provide enough information to establish comparative risk. The trial's original sample-size justification and intended power are not reported either. These limitations arise from the details available in the registry record and should not be mistaken for evidence that the unreported procedures or analyses were not conducted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Comparative Efficacy of Water & Indigo Carmine vs. Water or Air Method on Adenoma Detection Rate (ADR) - a Randomized Controlled Trial (RCT) — NCT01607255.
• Registry record last updated 2019-01-15; status last verified 2019-01.
• Results first posted 2019-01-15.
• 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

NCT01607255 is recorded as a completed, randomized, single-masked, parallel-group Phase 4 trial sponsored by the VA Office of Research and Development. Enrollment is listed as 480, with a start date of 2013-05-16 and primary completion date of 2017-06-30. The study compares water exchange, water exchange with indigo carmine, and the air method for screening colonoscopy.

The primary endpoint concerns participants with detected proximal diminutive adenomas, defined in the endpoint title as <10 mm, with a timeframe of 36 months. The registry record does not report primary outcome results or a statistical comparison. It lists serious adverse event counts by group and zero deaths in the group summaries, but does not provide enough context to determine comparative safety or causality. Analysis methods, missing-data procedures, analysis populations, and the trial's sample-size justification are not reported in the registry record.