Dose Rate Range Finding Study of Propofol for minimal-to Moderate Sedation on Upper & Lower Endoscopic Tests: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dose Rate Range Finding Study of Propofol for minimal-to Moderate Sedation on Upper & Lower Endoscopic Tests (NCT01189604), a randomized phase 2 study. The primary outcome is Modified Observers Assessment of Alertness/Sedation (MOAA/S) Score 2 Minutes From Beginning of Maintenance Period.

2. Clinical Question

This is a dose-rate range-finding question, not simply a comparison of one propofol regimen with placebo. The six propofol arms suggest an effort to examine multiple dose rates, but the registry record does not give those rates. Without both the assigned dose levels and the primary outcome results, readers cannot assess how sedation categories varied across the dose range or identify which maintenance rate the study favored.

3. Trial Design

The registry identifies NCT01189604 as a Phase II study. Its official title describes a multi-centre, single-blind, randomized, parallel-group Phase IIb dose-rate range-finding study. The registry lists randomized allocation, single masking and a parallel model. The masking entry does not identify which study participants or personnel were blinded, and further details of the randomization process are not reported in the registry record.

The study included a placebo arm and six arms named ICI35,868 (propofol). Each arm's detailed description is blank, so neither the assigned dose rates nor other arm-level treatment details are reported in the registry record. The planned clinical setting was gastrointestinal endoscopy, including polypectomy, with the aim of maintaining minimal-to-moderate sedation.

Enrollment is listed as 123. The recorded start is 2010-08, the primary completion is 2010-11, and the study status is completed. These dates and status describe the registry entry; they do not establish when results were analyzed or posted. The registry record does not report the allocation ratio, the number of participants assigned to each primary-outcome group, or a sample-size justification.

The primary outcome was a categorical summary of the MOAA/S score at 2 minutes from the beginning of the maintenance period. The record also names secondary outcomes concerning the Patient Satisfaction With Sedation Instrument questionnaire, blood concentrations of propofol, and MOAA/S at the end of the initiation period. There are five outcome measures recorded, but only these secondary outcome names and the primary outcome description are available in the record. A detailed statistical analysis plan is not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: The patients enrolled in this study were undergoing non-emergent standard esophagogastroduodenoscopy (EGD) or colonoscopy. Six patients were withdrawn from the study after enrollment but before randomization: 5 patients due to excess recruitment and one patient due to investigator's recommendation..

Only the first 6 of 7 groups are shown.

Overall Study

Reasons for not completing this period:

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.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Modified Observers Assessment of Alertness/Sedation (MOAA/S) Score 2 Minutes From Beginning of Maintenance Period, measured over 2 minutes from the beginning of the maintenance period.

The primary endpoint is the number of participants in each MOAA/S score category at 2 minutes from the beginning of the maintenance period. The registry describes MOAA/S as a 6-point ordinal scale of sedation: a score of 0 represents no response to a painful trapezius squeeze, while a score of 5 represents a ready response to a name spoken in a normal tone, indicating that the person is awake. The recorded categories are 0-1, 2-4 and 5.

Grouping scores turns the scale into a categorical endpoint. It retains a broad distinction among the listed levels of response while not retaining the exact score of every participant within a grouped category. The categories therefore describe the distribution of recorded sedation levels rather than a single average score. The endpoint is timed during maintenance, which is relevant to the stated aim of finding a rate for maintaining sedation, rather than measuring only sedation at the start of the procedure.

MOAA/S is used to assess level of alertness and response, concepts directly reflected in the study's minimal-to-moderate sedation aim. The registry record does not report the category counts, the number of participants with an evaluable score in each arm, or a comparison of those distributions. Consequently, it describes what the endpoint was intended to measure but does not report the observed primary endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a categorical primary endpoint and a randomized parallel-group design, but it does not report the statistical methods used to analyze the primary outcome. The concepts below explain general approaches to this kind of data; they should not be taken as a description of methods actually used in this trial.

What does the outcome represent?

The MOAA/S categories are ordered: the scale ranges from no response at 0 to awake at 5, and the primary endpoint groups scores as 0-1, 2-4 and 5. A categorical outcome is summarized by counts in categories, often accompanied by the corresponding proportions. For this trial, the registry's stated parameter is the number of participants. The record does not include the counts or proportions by arm.

Because these categories have an order, an analysis could in general use that ordering, or could treat the categories as nominal groups without relying on order. These approaches answer somewhat different questions. An ordered approach assesses how outcomes tend to shift across levels; a general comparison of category distributions asks whether the pattern differs between groups. Which approach, if any, was planned or used is not reported in the registry record.

How can groups be compared?

In general, a comparison of categorical outcomes can use a test of whether the distributions differ across groups, or estimates that contrast category probabilities between specified arms. With several arms, the choice of comparison matters: an overall test can assess whether any group differs, while pairwise contrasts address specific group pairs. A dose-ranging study may also examine whether results change systematically with dose, but that requires the assigned dose levels and a stated model or analysis strategy. Neither the dose rates nor the planned primary-outcome comparisons are reported in the registry record.

Random allocation can support a comparison of assigned groups, provided the analysis and outcome data are handled appropriately. It does not by itself specify the analysis population, address missing outcome measurements, or guarantee precise estimates. The registry record does not report whether the primary analysis followed assignment regardless of treatment received, whether it used another population, or how missing MOAA/S scores were handled.

What do precision measures add?

In general, a confidence interval gives a range of values compatible with the data and the assumptions of the analysis. Its width reflects precision: a wide interval leaves more uncertainty about the size and direction of an effect than a narrow interval. For categorical outcomes, intervals can be reported for group-specific proportions or for contrasts such as a difference between proportions. No primary-outcome confidence intervals or estimates are reported in the registry record, so neither the size of a contrast nor its precision can be assessed.

A significance test and its p-value address a question about compatibility between data and a specified null model. A p-value does not measure the probability that a treatment is effective, and it does not convey the practical importance of an observed contrast. Interpretation should therefore consider effect estimates and uncertainty as well as any test result. In this record, no primary-outcome test or estimate is listed.

What can the planning calculations say?

General sample-size calculations use assumptions about the outcome, target effect, significance level, allocation and analysis method. The planning illustration associated with the record is described as based on the 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. It is a planning illustration, not the trial's original design justification and not observed power. The record does not report a sample-size justification for the trial. It also does not report the primary outcome data needed to assess the observed effect in the registry record.

Those stated planning assumptions concern a two-arm illustration, whereas the trial has a placebo arm and six propofol arms. Such an illustration cannot, by itself, establish that the completed multi-arm study was designed to detect a particular difference or that its estimates are precise. The calculated planning values should be interpreted as prospective sample-size illustrations under their assumptions, not as evidence about the trial's observed findings.

Why are the dose rates and analysis plan important?

A dose-rate range-finding study generally needs interpretable links between assigned dose levels and measured outcomes. Without dose rates, a dose-response model or ordered trend cannot be reconstructed from arm labels. Without the analysis plan, it is not possible to know whether the intended primary inference was an overall group comparison, selected contrasts, a trend, or another approach. Neither detail is reported in the registry record. The posted information therefore supports explaining general statistical options, but not attributing a particular method or analysis decision to the trial.

10. Multiplicity, Missing Data and Analysis Populations

The study has multiple randomized arms, multiple recorded outcomes and a primary endpoint divided into three categories. Comparing many arms or outcomes can create multiplicity: when many hypotheses are tested, the chance of at least one apparently unusual result can increase. General strategies include defining a primary comparison in advance, using an overall test before selected comparisons, or adjusting inference across a family of tests. The registry record does not report whether any such strategy was planned or used.

The record names secondary measures for patient satisfaction, blood concentrations of propofol, and MOAA/S at the end of the initiation period. It does not report their results or analyses. It also does not specify how these measures relate to the primary endpoint in an inferential hierarchy. Without that information, the relative confirmatory or exploratory role of secondary outcomes is not reported in the registry record.

Missing outcome data can affect both the number of participants contributing to an analysis and the interpretation of the result. The registry record does not report missing MOAA/S scores, the number assessed in each arm, reasons for missingness, or a method for handling missing measurements. No analysis population is described, including whether participants were analyzed according to randomized assignment or according to treatment received.

The registry lists enrollment of 123, but does not give primary-outcome denominators by arm or identify the analysis population. The safety entries have their own at-risk counts, which should not be assumed to be the denominators for the primary endpoint. The trial's statistical analysis plan, multiplicity approach, and missing-data procedures are not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse-event counts and other adverse-event counts separately for each arm. For serious adverse events, the affected count is 0 in each listed arm. The at-risk counts are 20 in the placebo arm and in propofol Arms 2 through 5, and 10 in propofol Arms 6 and 7. These are the recorded counts for the safety entries; they do not provide a statistical comparison or establish that the underlying risk is identical across groups.

For other adverse events, the affected counts are 5 in the placebo arm, 0 in propofol Arm 2, 0 in Arm 3, 1 in Arm 4, 6 in Arm 5, 1 in Arm 6 and 2 in Arm 7. The corresponding at-risk counts are 20 for the placebo arm and propofol Arms 2 through 5, and 10 for propofol Arms 6 and 7. These counts describe the registry's recorded participants with an event; they should not be read as the number of all events if a participant could experience more than one.

No serious adverse-event terms are listed. Death counts are not reported in the registry record. The record does not provide event definitions, timing, severity details for other events, or an analysis comparing safety across arms. The arm-specific counts therefore describe what is recorded, without establishing causation or a treatment effect.

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

The registry record establishes that the study was a randomized, single-blind, parallel-group Phase II dose-rate range-finding study of propofol for sedation during gastrointestinal endoscopy, including polypectomy. It describes a primary endpoint based on MOAA/S categories measured at a specified time during maintenance. It also records a placebo arm, six propofol arms, enrollment of 123, and safety counts by arm.

Those design details do not establish what the primary outcome showed. The category counts, arm-specific primary-outcome denominators, estimates, confidence intervals and statistical tests are not reported in the registry record. It is therefore not possible from this record to determine how sedation categories differed across arms, whether there was a dose-related pattern, or how precise any group contrast was. The assigned dose rates are also absent, so the arms cannot be placed along a dose scale.

The safety entries report no serious adverse events among the listed at-risk participants and list other adverse events by arm. These are descriptive records, not proof that the groups had equivalent safety profiles or that any observed event was caused by study treatment. Death counts and further safety analyses are not reported.

In general, an endpoint can be relevant to a clinical objective while still being insufficient to support a comparative conclusion when its results are unavailable. A completed study status is not a substitute for posted outcome data. The record supports understanding the question the study set out to address and the broad structure of its design; it does not support a conclusion that propofol did or did not achieve a particular sedation level, nor does it identify an optimal maintenance dose rate.

13. Why This Trial Matters Statistically

This trial is statistically notable for the structure of its question. Rather than testing only one propofol regimen against placebo, it was described as a dose-rate range-finding study with six propofol arms. That design is intended to explore outcomes across a range, but interpreting it depends on knowing the dose rates attached to each arm. Those rates are not reported in the registry record, limiting any dose-response interpretation.

The primary endpoint also illustrates an important measurement choice. MOAA/S is an ordered scale, while the recorded primary outcome groups scores into three categories and reports participant counts. Grouping can make broad outcome patterns easier to communicate, but it does not retain the full score detail. A statistical analysis needs to align with the categorical structure and the question of interest, yet the registry does not report which method was used.

Several-arm studies raise questions about which comparisons matter and how uncertainty is controlled across them. Multiple outcomes and potential pairwise comparisons can complicate interpretation if the analysis plan is not available. In this case, the registry record lists outcomes but no analyses, primary results or multiplicity strategy. This makes transparent distinction between design information and outcome evidence especially important.

The case also shows why a completed status and an endpoint description cannot substitute for reported estimates. Without the primary category counts and uncertainty measures, readers cannot judge the observed pattern or its precision. The record is informative about the study's intended design and the limits of what can be concluded from its posted results, while leaving the central comparative question unanswered.

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 interpretation is that primary outcome results are not reported in the registry record. No category counts, arm-level estimates, inferential tests or confidence intervals are listed. The registry also records zero analyses. This prevents assessment of both the direction and precision of the primary comparison.

The dose-rate details are missing. Although the study is described as a range-finding investigation and includes six propofol arms, their descriptions do not state the dose rates. This prevents mapping outcomes to exposure levels and limits interpretation of any potential dose-response relationship. The allocation ratio and arm-level primary-outcome population are also not reported.

Details needed to assess potential bias and analysis choices are not available in the registry record. It identifies single masking but does not specify who was masked. The randomization procedure, analysis population, handling of missing primary scores, and statistical analysis plan are not reported. The registry does not describe the eligibility criteria or provide a fuller account of the participants contributing to the primary outcome.

The safety information is limited to arm-level affected and at-risk counts. Serious adverse-event terms are not listed, death counts are not reported, and further event definitions or analyses are unavailable. The posted safety counts should therefore be read descriptively, not as a complete comparative safety assessment.

These limitations concern what the registry record reports. They do not establish that the study failed to collect or analyze the relevant data; they mean that those details and results are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Dose Rate Range Finding Study of Propofol for minimal-to Moderate Sedation on Upper & Lower Endoscopic Tests — NCT01189604.
• Registry record last updated 2011-12-19; status last verified 2011-12.
• Results first posted 2011-12-13.
• 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

NCT01189604 is recorded as a completed randomized, single-blind, parallel-group Phase II study sponsored by AstraZeneca. Its official title describes a multi-centre Phase IIb dose-rate range-finding study of ICI35,868 (propofol) for minimal-to-moderate sedation during gastrointestinal endoscopic tests, including polypectomy. The registry lists enrollment of 123 and records a start of 2010-08 and primary completion of 2010-11.

The study included a placebo arm and six propofol arms. Its primary endpoint was the number of participants in MOAA/S categories 0-1, 2-4 and 5 at 2 minutes from the beginning of the maintenance period. The registry record does not report the primary outcome counts, dose rates, or analyses. Safety entries list no serious adverse events in the at-risk participants and report other adverse-event counts by arm; death counts are not reported.