Rapid Screening Phenotype Test To Evaluate CYP 2C19 Enzyme Activity Using Stable Isotope [13C]Pantoprazole: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Rapid Screening Phenotype Test To Evaluate CYP 2C19 Enzyme Activity Using Stable Isotope [13C]Pantoprazole (NCT00668902), a non-randomized na study. The primary outcome is DOBmax (Maximum Value of DOB).

2. Clinical Question

The study asks whether a breath test after stable-isotope pantoprazole can characterize CYP2C19 enzyme activity across groups defined by CYP2C19 genotype. The primary measure is DOBmax, the maximum change-over-baseline value in the breath carbon-dioxide isotope ratio. The registry record describes measurements before dosing and at several times afterward, but does not report DOBmax results for any group.

This is a phenotyping question: the breath test is intended to indicate enzyme activity in vivo. It is not a trial of whether pantoprazole improves a health outcome, and the record does not report a clinical outcome comparison. The stated rationale is that CYP2C19 activity can vary with inherited genetic variation and exposure to other medications. The study therefore focuses on measuring enzyme-related activity after a test dose, rather than evaluating a treatment strategy for a disease.

3. Trial Design

The registry identifies NCT00668902 as a completed study sponsored by Indiana University. It lists the phase as NA, allocation as non-randomized, masking as none, and the model as single group. Enrollment is listed as 25. The record gives a study start of 2007-03 and primary completion of 2008-12.

The intervention is [13C]pantoprazole. Participants were described in three CYP2C19 metabolizer categories: extensive metabolizers with the stated wild-type genotype, intermediate metabolizers heterozygous for deficient CYP2C19 alleles, and poor metabolizers homozygous for the described null alleles. These categories are used to organize enzyme-activity measurements. They should not be read as randomly assigned treatment groups or as a like-for-like control comparison.

The outcome description specifies breath measurements at baseline and after dosing at 2.5, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, and 120 min. The study aim is to assess CYP2C19 activity using the change in breath isotope ratio after [13C]pantoprazole. The brief summary additionally mentions blood samples, but the reported primary outcome is a breath-test measure.

The registry record does not report further details about recruitment, eligibility criteria beyond the healthy condition, dosing procedures, the number of participants in each primary-outcome analysis, or the rationale used to select enrollment. It also does not report whether participants completed every scheduled measurement. Because allocation was non-randomized and the design is recorded as single group, differences among metabolizer categories can describe patterns in the observed measurements, but do not constitute randomized treatment effects.

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 DOBmax (Maximum Value of DOB), measured over baseline and 2.5, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, and 120 min after dosing.

The primary endpoint is DOBmax, described as the maximum value of DOB. DOB is the change over baseline in the ratio of exhaled 13CO2 to 12CO2 after [13C]pantoprazole, relative to that ratio at baseline. The unit is listed as ratio, and the registry identifies the summary parameter as a mean with standard deviation.

The biological rationale in the record is that CYP2C19 O-demethylates [13C]pantoprazole. The resulting 13CO2 is exhaled and measured in breath. The record presents this process as a basis for using the breath response as a marker of CYP2C19 activity in vivo. Measuring the maximum response is intended to capture the largest observed change over the stated post-dose measurement schedule, rather than only a single prespecified time point.

In general, a continuous endpoint retains more information about the magnitude of a measurement than a simple classification of participants as having or not having an event. A group mean describes the average observed value, while a standard deviation describes how dispersed individual measurements are around that average. Neither summary alone shows the full distribution or whether groups differ beyond what could plausibly arise from sampling variability.

The registry record does not report DOBmax means, standard deviations, participant counts contributing to the endpoint, confidence intervals, or a statistical test. Therefore, the endpoint definition and measurement rationale can be described, but the magnitude and precision of the observed breath-test responses cannot be evaluated from the posted outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary measure, DOBmax, summarized as a mean and standard deviation. Understanding what those summaries can convey helps distinguish the planned endpoint from evidence about its observed values. In this record, the outcome values and inferential analyses are not reported, so the methods can be explained conceptually without implying that a particular analysis was conducted.

What does a mean describe?

In general, the mean is the arithmetic average of the observations included in an analysis. For a breath-test endpoint, it would describe the average DOBmax among the participants whose measurements were used for that group or analysis. A mean is sensitive to unusually high or low observations, so it is most informative when considered alongside the distribution and the number of observations. The registry record identifies the mean as the summary parameter but does not report the resulting means or the analysis counts.

What does a standard deviation describe?

In general, a standard deviation describes the spread of individual measurements around their mean. A smaller standard deviation indicates that observations are more closely clustered around the average; a larger one indicates greater dispersion. It is not the same as a confidence interval, and it does not directly quantify uncertainty in the estimated mean. That uncertainty also depends on the amount of information in the analysis and on the assumptions used. The registry record states that standard deviation was the dispersion measure, but does not report any standard deviations.

Why use a continuous breath-test measure?

The endpoint is based on ratios of exhaled 13CO2 and 12CO2, expressed as change over the baseline ratio. A continuous measurement can retain variation in the breath response rather than reducing observations to a simple category. The record identifies the maximum value of DOB as the primary outcome, with measurements at baseline and a sequence of post-dose times. In general, using a maximum across repeated measurements makes the endpoint dependent on the measurement schedule and on the reliability of the measurements at each time. The registry record does not explain how a maximum would be handled if a measurement were missing or invalid.

How would uncertainty usually be assessed?

In general, a confidence interval gives a range of values compatible with an estimate under the assumptions of the statistical method. It can help readers judge precision, while a p-value addresses how compatible the observed data are with a specified null hypothesis under a statistical model. Neither can be interpreted without knowing the analysis, the observations included, and the assumptions. The record lists no analyses and reports no confidence intervals or p-values for DOBmax. It is therefore not possible to describe the precision of the endpoint estimate or the statistical evidence for contrasts among metabolizer groups.

What does the study structure imply for comparisons?

The study is listed as non-randomized, unmasked, and single group. The metabolizer categories are defined by genotype descriptions, not assigned by a random allocation process. In general, a comparison between such categories is an observational contrast. Differences can reflect the biological grouping of interest, but may also be related to other characteristics that differ between groups. Randomization is one method of balancing factors on average between assigned interventions; it is not described for this study. The record does not report an adjusted model or a set of covariates used to account for potential differences between categories.

What is meant by over-dispersion?

In general, over-dispersion means that observed variability is greater than a statistical model expects. It is especially discussed for count outcomes, where a model may assume a particular relationship between the mean and variance. DOBmax is described as a continuous measure, and the registry record does not identify a count model or report evidence of over-dispersion. The concept is not a reported feature of this study; it illustrates why model assumptions should match the kind of endpoint and its observed distribution.

What can be inferred from the planning assumptions?

The registry record includes a description of a planning illustration based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect, and distinguishes participant counts per arm from total event counts for time-to-event settings. These are general planning assumptions, not reported results from this study’s design process. The record does not provide the illustration’s calculated sample-size values in the registry record for this account, nor does it establish that this was the study’s original sample-size justification. It would be inappropriate to treat planning calculations as observed power or as evidence that the completed study had adequate precision.

Overall, the registry supplies enough information to explain the endpoint and broad design, but not enough to reproduce or evaluate an outcome analysis. The statistical analysis plan, model specification, handling of missing measurements, and prespecified contrasts are not reported in the registry record. Accordingly, no unadjusted re-calculation or sponsor analysis can be described from the posted primary-outcome information.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("EM of CYP2C19", "IM of CYP2C19", "PM of CYP2C19")
n   <- c(10, 10, 5)
m   <- c(4.44, 3.49, 0.92)
sp  <- c(1.79, 1.18, 0.18)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  EM of CYP2C19  10  4.440  1.790  3.160  5.720
CARM  IM of CYP2C19  10  3.490  1.180  2.646  4.334
CARM  PM of CYP2C19  5  0.920  0.180  0.697  1.143

11. Multiplicity, Missing Data and Analysis Populations

The primary outcome description includes repeated breath measurements: baseline and 2.5, 5, 10, 15, 20, 25, 30, 40, 50, 60, 90, and 120 min after dosing. The primary endpoint is the maximum value of DOB across the measurement schedule. This definition indicates that multiple time points contribute to the endpoint, but the registry record does not explain the operational rule used to select the maximum, how measurements were quality-checked, or how an incomplete series would be handled.

The record lists one outcome measure and no analyses. It does not report a statistical analysis plan, a hierarchy of endpoints, prespecified comparisons among metabolizer groups, or any adjustment for multiple testing. In general, multiplicity becomes relevant when several hypotheses or contrasts are examined, because repeated testing can increase the chance of a false-positive finding if no suitable strategy is used. The posted record does not establish which, if any, comparisons were tested, so no multiplicity procedure can be attributed to this study.

Missing-data methods and analysis populations are also not reported in the registry record. There is no stated intention-to-treat or per-protocol population, no endpoint-specific analysis count, and no account of participants with incomplete breath measurements. The enrollment listing is not enough to determine how many observations contributed to each reported estimate, particularly because no estimates are posted. The registry record likewise does not state whether any participants were excluded from analysis or how exclusions were defined.

In general, missing measurements can affect both the amount of information available and the interpretation of an estimate, especially if the likelihood of a missing measurement is related to the underlying response. No missingness pattern or sensitivity analysis is reported. The absence of a reported method should not be interpreted as evidence that there were no missing data or that a particular analysis population was used.

12. 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 0% reporting threshold.

The registry’s adverse-event listing gives separate CYP2C19 groups and reports zero participants affected by serious adverse events in each listed group. The numbers at risk for serious adverse events are 10 for extensive metabolizers, 10 for intermediate metabolizers, and 5 for poor metabolizers. The listing also reports zero participants affected by other adverse events, with the same group-specific numbers at risk.

These figures describe the posted registry safety outcome, not a comparison of randomized treatments. The metabolizer groups are genotype-defined, and the study is non-randomized. The registry record does not report a comparator group receiving a different intervention, nor does it provide event descriptions in the top serious-event terms listing.

Zero affected participants in the posted listing means that no events are recorded in those categories for the participants listed as at risk. It does not establish that an event is impossible, nor does it quantify risk beyond this study’s observed participants. With no comparison group and no additional safety-analysis details reported, the figures do not support a causal comparison or a broad estimate applicable to other populations.

Deaths are recorded as null rather than as a numerical count. A null entry is not the same as a reported zero, so the death count is not reported in the registry record. The safety data should therefore be read narrowly: the listed serious and other adverse-event counts are zero, while the death count and further event detail are not reported.

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

This study is designed to examine a measurement: whether the breath response after [13C]pantoprazole can characterize CYP2C19 activity across genotype-defined metabolizer categories. Its primary endpoint, DOBmax, is a maximum change-over-baseline isotope ratio. The record explains why the breath signal is biologically relevant, but it does not post the actual endpoint values.

That distinction matters. A stated mechanism and a defined endpoint explain what researchers intended to measure; they do not show the observed size of a response, whether groups differed, or how precisely any difference was estimated. Because no primary-outcome means, standard deviations, confidence intervals, or analyses are reported, the posted record cannot establish the degree to which DOBmax varied across the metabolizer categories.

The study also does not test whether a particular medication should be prescribed, whether the breath test improves patient outcomes, or whether using the test changes drug-related harms. The brief summary describes the possibility that enzyme activity and drug response can vary, but no clinical treatment comparison or patient-outcome analysis is reported. A phenotype measure may be relevant to later research, but its clinical usefulness cannot be established from the endpoint definition alone.

The non-randomized, single-group structure means the genotype-defined categories should not be treated as assigned treatment groups. Even if group outcome estimates were available, an observed contrast would not by itself show that a clinical intervention caused a difference. The registry record also does not report validation against an independent measure, diagnostic accuracy, or decision-making performance.

The limited safety listing records zero serious and other adverse events among the listed participants at risk, but the death entry is null. These entries describe the posted record and do not establish the absence of all possible harms. Overall, the record documents a small completed phenotyping study’s aim, measurement schedule, and broad design. It does not report the statistical results needed to judge the primary measurement’s observed performance or its clinical implications.

14. Why This Trial Matters Statistically

Statistically, the study is useful to consider because it separates a biological measurement question from a treatment-effect question. Its endpoint is a continuous breath-test response intended to reflect CYP2C19 activity after a stable-isotope substrate. The genotype-defined categories offer a framework for studying whether the measurement varies with metabolizer status. That is a different question from whether an assigned treatment improves a clinical outcome.

The endpoint also illustrates how a summary measure depends on measurement design. DOBmax is defined from repeated post-dose breath measurements relative to baseline. The selected maximum can reflect the timing and quality of measurements, so a transparent description of how the series is handled is important. Although the registry provides the measurement schedule and endpoint definition, it does not report the rules for incomplete series or the numerical results.

The non-randomized structure is another important statistical feature. Genotype categories are not randomized arms. This makes it essential to distinguish descriptive group patterns from causal claims and to know whether relevant differences between groups were addressed in an analysis. The registry record lists no analyses and does not report adjusted estimates or potential covariates.

Finally, this record illustrates the limits of interpreting a completed study from design information alone. Enrollment and a clearly described endpoint do not substitute for outcome estimates, analysis counts, and measures of uncertainty. Without these, readers cannot assess the size, variability, or precision of the observed breath response. The study’s stated biological rationale remains distinct from empirical evidence about how well the endpoint performed in the enrolled participants. The posted record is therefore informative about the intended question and measurement approach, while leaving the central statistical result unreported.

15. 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 principal limitation for interpreting the study is that the registry record does not report the primary endpoint results. DOBmax is defined and its measurement schedule is described, but group means, standard deviations, confidence intervals, and analysis counts are not reported. The record lists no analyses. This prevents assessment of the observed breath-test response, variability, precision, and any statistical contrast across metabolizer categories.

The record also gives limited information about the study population. Healthy participants are identified, but further eligibility details and participant characteristics are not reported in the registry record. Although the enrollment listing is 25, endpoint-specific denominators and completion of the breath-measurement schedule are not reported. The record does not describe missing-data handling, exclusions, or analysis populations.

The design is non-randomized and listed as single group, with no masking. Metabolizer categories are defined by genotype rather than allocated as interventions. Accordingly, category differences, if available, would be observational. The record does not report adjustments for other characteristics that might differ across categories, or a statistical model for analyzing the outcome.

The endpoint is the maximum value across measurements taken at several post-dose times. The record does not specify how the maximum was determined in cases of incomplete measurements, how breath-test measurements were checked, or how repeatability was assessed. It also does not report validation against an independent reference measure or diagnostic performance.

Safety information is limited to the listed adverse-event counts. The death field is null, and further event details are not reported. The record does not provide a clinical outcome comparison or evidence about the effect of using this measurement to guide care. These omissions limit both statistical interpretation and conclusions about broader clinical relevance.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Rapid Screening Phenotype Test To Evaluate CYP 2C19 Enzyme Activity Using Stable Isotope [13C]Pantoprazole — NCT00668902.
• Registry record last updated 2014-12-17; status last verified 2014-12.
• Results first posted 2014-12-17.
• 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.

19. Record Summary

NCT00668902 is a completed, non-randomized, unmasked, single-group study sponsored by Indiana University. The registry lists enrollment of 25, the phase as NA, a start of 2007-03, and primary completion of 2008-12.

The study assessed CYP2C19 activity in healthy participants using [13C]pantoprazole and a breath-test measure. The primary endpoint is DOBmax, the maximum change-over-baseline value of the exhaled 13CO2/12CO2 ratio, summarized as a mean with standard deviation. The record describes extensive, intermediate, and poor metabolizer categories and measurements from baseline through 120 min after dosing.

The registry record does not report primary endpoint values, endpoint analysis counts, inferential analyses, confidence intervals, or missing-data methods. The safety listing records zero serious and other adverse events in the listed groups; deaths are recorded as null. The posted information therefore describes the study question and measurement approach but does not report the primary statistical results.