Modernization of in vivo-in Vitro Oral Bioperformance Prediction and Assessment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Modernization of in vivo-in Vitro Oral Bioperformance Prediction and Assessment (NCT02806869), a randomized na study. The primary outcome is Average Duodenal Fluid pH in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen.

2. Clinical Question

The study’s broader objective was to examine in vivo dissolution and systemic absorption of ibuprofen under fed and fasted conditions through direct sampling of stomach and small intestinal contents. The registry describes the study as a research effort intended to inform physiologically relevant in vitro models. The posted primary endpoint focuses specifically on duodenal fluid pH, while the secondary endpoints address maximum duodenal ibuprofen concentration and plasma concentration-time exposure. These measures characterize different parts of the drug’s passage through the gastrointestinal tract and into the circulation. The record does not state a formal hypothesis or a threshold that would define a meaningful pH difference.

3. Trial Design

The registry describes a randomized, open-label, parallel study with two arms. One arm studied ibuprofen in the fasting state; the other studied ibuprofen after Pulmocare. The listed enrollment was 48. For the primary endpoint, the posted analysis includes 20 participants in the fasting arm and 17 in the fed arm. The registry does not explain why these analysis counts differ from the enrollment count.

Each arm description specifies two study visits. In the fasting arm, a single 800 mg ibuprofen tablet was given with 250 mL of water containing phenol red at each visit. In the fed arm, two 8.0 oz (236.6 mL) cans of Pulmocare preceded the single ibuprofen dose, which was taken with 250 mL of water containing phenol red. Both arm descriptions specify a washout period of at least 7 days between visits. The record does not describe the visit order, whether any additional procedures differed between visits, or how the random allocation sequence was generated or concealed.

Masking is listed as none. The study therefore was not described as blinded in the registry, but the record does not detail which study personnel knew the assigned condition. The study is listed as completed, with a start of 2015-01 and primary completion of 2016-11. Its phase is listed as NA. The sponsor is the University of Michigan, and the listed condition is Human Gastrointestinal Physiology Data.

The primary endpoint is continuous: average duodenal fluid pH, reported as a mean and standard deviation for measurements taken from time 0 to 7 hours. Two secondary outcomes are posted, both comparing fasting and fed participants: maximum duodenal fluid concentration of ibuprofen over time 0 to 7 hours, and average area under the plasma concentration-time curve over time 0 to 24 hours. The registry record does not describe a formal statistical analysis plan, a sample-size justification for the original trial, or an intended analysis population beyond the endpoint-specific participant counts.

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.

First Intervention (1 Day)

Washout (7 Days)

Second Intervention (1 Day)

Analysis population for the primary outcome, as defined in the registry: Overall Number of Participants Analyzed equals the number of participants who completed the First intervention plus the number of participants who completed the Second Intervention. For Arm #1: Overall Number of Participants Analyzed=13+7=20. For Arm #2: Overall Number of Participants Analyzed=12+5=17.

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: Overall Number of Baseline Participants equals the number of participants who completed the First intervention

6. Primary Endpoint

The registry lists the primary outcome as Average Duodenal Fluid pH in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen, measured over from time 0 to 7 hours.

The primary endpoint is the average pH of duodenal fluid from time 0 to 7 hours. The registry says pH was measured at multiple time points during that period and that the reported value is the mean and standard deviation of duodenal fluid pH. This endpoint summarizes the local fluid environment in the duodenum, where drug dissolution and movement through the gastrointestinal tract are relevant to the study’s research objective.

As a continuous measure, pH can be described by a group mean and by the spread of observations around that mean. Comparing means gives a concise account of how the average measured pH differed between the fasting and fed conditions. It does not show the full pattern of measurements over time, whether the groups differed at particular time points, or how pH related to individual participants’ ibuprofen concentration measurements. Those details are not reported in the registry record.

The endpoint is used as a physiological characterization, not as a direct clinical outcome. A difference in average duodenal pH alone does not establish a difference in drug dissolution, absorption, or clinical effect. The study also posted measures of duodenal ibuprofen concentration and plasma exposure, which address other aspects of the research question. The registry record does not identify a minimum pH difference considered important, or state that pH is a validated substitute for a clinical outcome.

7. Results Posted in the Registry

• Arm #2 - Fed State, 2 Study Visits: mean 5.36 versus 5.12 on control; difference 0.24 (95% CI -0.74 to 1.22), standardized effect d = 0.16; z-test p = 0.631.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Maximum Duodenal Fluid Concentration of Ibuprofen in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Arm #2 - Fed State, 2 Study Visits: mean 155.00 versus 217.00 on control; difference -62.00 (95% CI -191.79 to 67.79), standardized effect d = -0.30; z-test p = 0.349.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Arm #2 - Fed State, 2 Study Visits and the control. The interval gives the range of effects that remain compatible with the data.

Average Area Under the Plasma Concentration-time Curve (AUC) in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Arm #2 - Fed State, 2 Study Visits: mean 229.00 versus 242.00 on control; difference -13.00 (95% CI -66.43 to 40.43), standardized effect d = -0.16; z-test p = 0.633.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Arm #2 - Fed State, 2 Study Visits and the control. The interval gives the range of effects that remain compatible with the data.

The two secondary measures address related but distinct stages of the study’s research question. Maximum duodenal fluid ibuprofen concentration describes a local gastrointestinal concentration over time 0 to 7 hours. Plasma AUC describes systemic exposure over time 0 to 24 hours. Both are continuous outcomes, and each compares the fasting and fed arms. Their units and observation periods differ, so their numerical estimates should not be compared directly with the primary pH estimate or with one another.

Across the posted results, the secondary summaries do not provide a clear, precise contrast between conditions: their recalculated intervals extend across zero, as does the primary comparison’s interval. This broad pattern is consistent with the primary result in the limited sense that none of the posted comparisons precisely establishes a directional difference. It does not show that the endpoints are interchangeable, that they measure the same underlying process, or that one result explains another. Individual-level links among pH, duodenal concentration, and plasma exposure are not reported in the registry record.

The registry lists no reported analyses for the secondary outcomes. Their mean differences, intervals, and unadjusted p-values are recalculated from the posted summary statistics. These results should therefore be treated as descriptive, unadjusted comparisons rather than as documented sponsor analyses. The record does not describe adjustment for other factors, repeated measurements, or a prespecified hierarchy among outcomes.

When several outcomes are examined, the chance of finding at least one apparently notable result can increase if each is assessed separately without accounting for multiplicity. This is a general statistical concern, not a claim that a particular false-positive result occurred in this study. Because no multiplicity strategy is reported, unadjusted secondary results carry less weight as confirmatory evidence. They can be useful for understanding the range of measurements collected and for motivating further study, but the registry record does not establish that they were intended as independent confirmatory tests.

The secondary outcomes also do not replace the primary endpoint. The pH result characterizes duodenal fluid acidity, while the concentration and AUC results describe ibuprofen measurements in gastrointestinal fluid and plasma. A complete account of how these outcomes were selected, prioritized, and analyzed is not reported in the registry record. Consequently, the overall pattern is informative as a descriptive set of observations, but it is not a formal test of a unified mechanistic model.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Maximum Duodenal Fluid Concentration of Ibuprofen in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen
• Average Area Under the Plasma Concentration-time Curve (AUC) in Fasted Compared to Fed Participants Administered a Single Dose of Ibuprofen

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is a continuous variable, so its posted summaries are means and standard deviations. A mean describes the average observed pH in an arm. A standard deviation describes how dispersed the measurements are around that arm’s mean; it is not the uncertainty in the mean itself. The fasting mean was 5.12 with standard deviation 1.64, and the fed mean was 5.36 with standard deviation 1.4.

The comparison is expressed as the fed mean minus the fasting mean. The recalculated unadjusted estimate is 0.24. This direction convention matters: a positive estimate means the posted fed-arm mean is higher than the fasting-arm mean. It does not by itself indicate that the difference is important or that the fed condition caused the difference. The recalculation uses the posted summary statistics and is not a reported adjusted model.

A confidence interval describes a range of values compatible with the observed estimate under the assumptions of the calculation. Wider intervals indicate less precision; narrower intervals indicate more precision. The primary comparison’s interval crosses zero, meaning that it includes a null difference and values on either side. The registry does not state the confidence level for this interval, so it should not be assigned one based on the information in the record. The interval is a measure of uncertainty about the mean difference, not a range expected to contain a fixed proportion of individual participants’ pH values.

The unadjusted p-value for the recalculated primary comparison is 0.631. In general, a p-value describes how incompatible the observed data are with a specified null model, under the model’s assumptions. It is not the probability that the null hypothesis is true, nor does it quantify the probability that a result will be reproduced. Because this value is recalculated from posted summary statistics and the record lists no reported analyses, it should not be treated as a sponsor-reported result or as evidence that a prespecified analysis was followed.

The trial has repeated study visits within each arm, and the endpoint description refers to measurements at multiple time points. In general, repeated observations from the same participant are related rather than independent. Accounting for that dependence can matter when estimating uncertainty or describing changes over time. The registry’s posted endpoint summary is an arm-level mean and standard deviation; it does not provide the individual-level data, time-specific summaries, or statistical model needed to assess how within-participant and within-visit dependence was handled. Whether the reported summary combines the visits in a particular way is not reported in the registry record.

What does the standard deviation tell us?

The standard deviation reflects variation in measured pH among the observations contributing to an arm’s summary. It can help readers see whether a mean is accompanied by tightly grouped or widely dispersed values. It does not reveal the shape of the distribution, identify outliers, or distinguish variation between participants from variation across visits or time points. Those details require information not reported in the registry record. The two arm standard deviations are not standard errors and should not be read as confidence limits for the means.

Why distinguish the recalculation from a reported analysis?

A recalculation from summary statistics is useful for giving a consistent, transparent comparison, but it cannot reproduce an analysis that uses unavailable participant-level data or a specified model. Adjustment for baseline features, repeated measurements, or other design details could affect an inferential estimate. The record lists zero reported analyses, so no sponsor analysis can be compared with this recalculation. The discrepancy indicator is false; nevertheless, the posted comparison remains a recalculation rather than a reported analysis. If the sponsor’s own analysis were reported and differed, the sponsor analysis would take precedence for describing the trial’s prespecified result.

How should dispersion be understood?

Over-dispersion, in general, means that observed variability is greater than an analysis model expects. If a model understates variability, its standard errors can be too small and its intervals too narrow. This is a general statistical concern, not a finding established by the registry data. The posted standard deviations show spread, but the record does not report a model-based assessment of dispersion, diagnostics, or an analysis that would establish over-dispersion. The endpoint is continuous, and the registry does not report that a count model or a particular distributional assumption was used.

More generally, statistical estimates depend on both the data and the analysis assumptions. Randomization can support a comparison of assigned conditions when its implementation and analysis are appropriate, but the registry does not give enough detail to assess sequence generation, allocation concealment, or the full handling of repeated observations. The absence of those details does not establish that the procedures were inadequate; it means they cannot be evaluated from the registry record.

11. Confidence Intervals and Precision

Precision concerns how tightly the data locate an estimated difference. The primary estimate is a mean difference of 0.24 for fed compared with fasting, based on 20 and 17 analyzed participants. Its interval crosses zero, extending from a negative value to a positive value. Thus the estimate does not precisely determine whether the population mean difference is positive, negative, or close to zero. The interval also shows that the point estimate should not be treated as an exact value for the underlying difference.

The posted arm standard deviations, 1.64 for fasting and 1.4 for fed, describe variability in the measured pH values. The comparison interval incorporates uncertainty in the difference between the means; it is not interchangeable with either arm’s standard deviation. Since the record does not provide participant-level observations or time-specific summaries, the influence of within-person variation and the pattern of pH over time cannot be assessed from the posted summary.

The interval is a recalculated unadjusted interval based on the posted summaries. The registry does not report the sponsor’s analysis, a confidence level, or a prespecified model for the primary comparison. Those omissions limit the interpretation of the interval: it conveys uncertainty under the recalculation’s assumptions, not a complete account of uncertainty under an undocumented analysis plan. The p-value of 0.631 is also recalculated and should be read alongside the effect estimate and interval rather than as a stand-alone verdict.

A broad interval can be compatible with a range of possible effects. It does not prove that no difference exists, and a point estimate near zero does not establish equivalence. The registry does not state an equivalence margin or a minimum meaningful difference for pH. In practical terms, the primary posted comparison is not precise enough to settle the size or direction of a population difference, and the available record does not define a threshold against which that uncertainty could be judged.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. The registry’s planning illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It uses the observed effect as its reference, then considers detecting 100%, 75%, or 50% of that observed effect. These are planning assumptions for an illustration computed from the observed effect; the original trial’s sample-size justification and design assumptions are not reported in the registry record.

For the primary pH comparison, planning for 100% of the observed effect gives 643 participants per arm for 80% power and 860 participants per arm for 90% power. Planning for 75% of the observed effect gives 1,142 participants per arm for 80% power and 1,529 participants per arm for 90% power. Planning for 50% of the observed effect gives 2,569 participants per arm for 80% power and 3,439 participants per arm for 90% power.

In plain language, the 80% power column describes the per-arm sample size that the stated planning calculation associates with an 80% chance of detecting the chosen effect if the assumptions hold and that effect is present. The 90% column makes the corresponding calculation for a higher chance of detection. A smaller target effect is harder to distinguish from random variation, so the planning calculation requires more participants per arm as the target effect becomes smaller.

These values are not observed power. They are prospective planning illustrations based on the observed effect, not evidence about the probability that this completed trial detected an effect or about the original investigators’ design rationale. They also depend on the stated assumptions and should not be read as guarantees that a future study of that size would produce a particular result.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.240; pooled standard deviation σ = 1.535.
2. n = 2 × (1.96 + 0.842)² × 1.535² / 0.240² = 642.1, rounded up to 643 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.24                      # observed difference in means
sigma <- 1.53494904522221                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2806869)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 643 (80% power), 860 (90% power)
 75% of observed effect: n per arm = 1,142 (80% power), 1,529 (90% power)
 50% of observed effect: n per arm = 2,569 (80% power), 3,439 (90% power)
power.t.test: 643.1 
Simulated power at n = 643 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary endpoint and two secondary outcomes, but does not report a statistical analysis plan or a multiplicity adjustment. It is therefore not known whether the trial used a prespecified testing sequence, adjusted the interpretation of multiple comparisons, or treated the secondary outcomes as exploratory. When multiple outcomes are tested, unadjusted p-values can overstate the strength of evidence if each result is interpreted as a separate confirmatory finding. This general issue is relevant to the posted secondary comparisons, whose analyses are recalculated and unadjusted.

The record does not report how missing endpoint observations were handled, whether any participants were excluded from particular analyses, or whether missingness was assessed by arm or by visit. It also does not report imputation, sensitivity analyses, or assumptions about why observations might be missing. The primary endpoint’s posted counts are 20 in the fasting arm and 17 in the fed arm, while enrollment is listed as 48. The reason for the difference is not reported in the registry record; it should not be attributed to withdrawal, protocol deviations, or missing data without further information.

The primary endpoint description defines the analyzed population as participants who completed the first intervention plus participants who completed the second intervention. The arm-specific wording gives 13+7=20 for the fasting arm and begins 12+5= for the fed arm, while the posted fed-arm analysis count is 17. The record does not explain the incomplete expression or clarify how completion at each visit maps to the final endpoint analysis. It does not describe an intention-to-treat population, a per-protocol population, or another named analysis set.

In general, the interpretation of randomized comparisons depends on retaining the integrity of the assigned groups and handling missing outcomes appropriately. The registry gives the allocation type as randomized, but details about sequence generation, concealment, deviations, and analysis by assigned group are not reported. These missing details prevent a full assessment of risk from selective analysis or missing outcomes. They do not establish that bias occurred; they identify limits on what can be checked from the public record.

The record also does not state whether subgroup analyses or interim analyses were planned or conducted. No conclusions should be drawn about those procedures from their absence in the posted record. Overall, multiplicity and missing-data methods are not reported in the registry record, so the posted results are best interpreted as endpoint-specific summaries with recalculated unadjusted comparisons and incomplete information about the analysis population.

15. 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.

Most frequent non-serious adverse event terms

The registry lists serious adverse events as zero among 24 participants at risk in the fasting arm and zero among 24 participants at risk in the fed arm. These figures describe the serious-event counts in the posted safety record. The record does not list any serious adverse-event terms.

For other adverse events, the registry lists zero among 24 participants at risk in the fasting arm and one among 24 participants at risk in the fed arm. The type and details of that event are not reported in the registry record. Death counts are not reported in the record; a missing death count should not be interpreted as a count of zero.

These safety figures are counts within the listed at-risk groups, not estimates of comparative risk adjusted for exposure time or other factors. The record does not describe event collection procedures, severity grading, relatedness assessment, or the timing and duration of safety monitoring. With the available information, the counts can be reported descriptively but do not support a detailed comparison of safety between conditions.

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

The posted primary result describes average duodenal fluid pH in the analyzed fasting and fed groups over time 0 to 7 hours. The group means were 5.12 and 5.36, and the recalculated unadjusted mean difference was 0.24 for fed compared with fasting. The interval spans negative and positive values, while the recalculated unadjusted p-value was 0.631. Taken together, these statistics indicate substantial uncertainty about the direction and size of the population difference.

The result does not establish that the conditions have identical effects. A non-zero difference remains compatible with the interval, and the registry does not report an equivalence margin or a threshold defining a negligible pH difference. The result also does not show that the fed condition produces a meaningful pH change. No clinical importance threshold is reported, and pH is a physiological measure rather than a direct clinical outcome.

Nor does the primary result alone establish whether ibuprofen dissolved differently, how much was absorbed, or whether systemic exposure differed. The registry posts separate secondary measures for maximum duodenal ibuprofen concentration and plasma AUC, but those are distinct endpoints. The posted summaries do not demonstrate that a change in pH caused any change in either secondary measure. Participant-level relationships and a formal mechanistic analysis are not reported.

The study’s stated research objective was to evaluate in vivo dissolution and systemic absorption under fed and fasted conditions and to inform physiologically relevant in vitro models. The posted outcome summaries provide observations relevant to that objective, but the registry record does not report a formal validation of an in vitro model or a predictive-performance result. It also does not report the full statistical plan, missing-data methods, or analysis of repeated observations. Such information would be needed to assess the analysis comprehensively.

Accordingly, the most defensible reading is limited: the analyzed groups had the reported average pH values, and the recalculated comparison is imprecise. The results should not be generalized beyond the study population and procedures without additional evidence. They do not establish a treatment recommendation, a clinical benefit, or a lack of effect. They describe a small set of posted physiological and concentration summaries, with important design and analysis details not reported in the registry record.

17. Why This Trial Matters Statistically

This trial is statistically interesting because it connects an in vivo physiological measurement with questions about drug dissolution and absorption. Direct sampling of gastrointestinal contents is part of the study’s stated objective, while the primary endpoint summarizes duodenal fluid pH and the secondary endpoints describe ibuprofen concentration in duodenal fluid and plasma exposure. These measurements address related stages of a process, but their relationships cannot be established from arm-level means alone.

The design also makes the distinction between a study’s biological aim and its statistical endpoint important. The primary endpoint is average pH, not a direct measurement of model performance or clinical outcome. A finding about average pH cannot, on its own, validate a predictive laboratory model. The record’s objective is broader than the single primary comparison, so it is useful to keep the endpoint-specific evidence separate from the overall research motivation.

The posted summaries illustrate why estimates, intervals, and variability should be read together. The primary mean difference is 0.24, but the interval crosses zero and the groups show substantial within-arm dispersion. The recalculated p-value is 0.631. These statistics do not establish that the true difference is zero; they indicate that the available summary provides limited precision for identifying the difference’s direction and size.

The registry also illustrates the limits of public summary records. It lists randomization, arms, endpoints, and analyzed counts, but does not report a statistical analysis plan, a sponsor-reported inferential analysis, missing-data methods, or multiplicity procedures. This means readers can describe the posted observations and understand the recalculation, while remaining cautious about undocumented decisions and the handling of repeated measurements.

Finally, the planning illustration makes clear how a small observed effect can translate into large prospective sample-size requirements under stated assumptions. Those figures are not the original trial’s justification. Keeping planning calculations separate from the completed study’s observed results is essential: the former are illustrations for future design choices, while the latter are summaries of the analyzed participants.

18. 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 primary comparison includes 20 analyzed participants in the fasting arm and 17 in the fed arm, compared with a listed enrollment of 48. The registry record does not explain why the analyzed counts differ from enrollment or whether the difference reflects missing measurements, exclusions, or another reason. This limits assessment of the analysis population and of possible selection effects.

The endpoint is measured repeatedly over time, and each arm has two study visits. However, the record reports an overall mean and standard deviation rather than visit-specific or time-specific results. It does not describe whether summaries were based on individual observations, participant averages, or a model that accounted for within-participant dependence. The recalculated comparison therefore cannot resolve how these repeated features affected uncertainty.

Randomization is listed, but the method used to generate the allocation sequence, conceal allocation, and handle deviations from assignment is not reported in the registry record. Masking is listed as none. The record also does not describe whether measurement procedures were standardized across visits or whether personnel assessing outcomes were aware of study condition. These gaps limit evaluation of potential sources of bias without showing that bias occurred.

The original sample-size rationale, prespecified hypotheses, statistical analysis plan, missing-data methods, multiplicity approach, and interim-analysis plans are not reported. No sponsor-reported inferential analysis is posted for the primary or secondary outcomes. The presented comparisons are recalculated from summary statistics, so they may not reflect unavailable analyses using participant-level data or a specified model.

Finally, the study’s stated objective includes in vivo dissolution, systemic absorption, and informing in vitro models, but the posted outcomes do not include a reported formal validation of model prediction. The registry record also does not state a threshold for a meaningful pH difference. These limitations constrain interpretation of the physiological comparisons and the broader modeling objective.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Modernization of in vivo-in Vitro Oral Bioperformance Prediction and Assessment — NCT02806869.
• Registry record last updated 2017-12-08; status last verified 2017-11.
• Results first posted 2017-12-08.
• 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.

22. Record Summary

The registry record describes a completed randomized, open-label, parallel study sponsored by the University of Michigan. It lists enrollment of 48 and compares a fasting ibuprofen arm with a fed ibuprofen arm in healthy adult volunteers. Each arm description includes two study visits separated by a washout period of at least 7 days.

The primary endpoint is average duodenal fluid pH from time 0 to 7 hours. The posted analyzed counts are 20 in the fasting arm and 17 in the fed arm. The recalculated unadjusted mean difference is 0.24, with an interval that crosses zero and an unadjusted p-value of 0.631. The registry lists two secondary outcomes: maximum duodenal fluid ibuprofen concentration and average plasma AUC.

No sponsor-reported analyses, statistical analysis plan, original sample-size justification, multiplicity procedure, or missing-data method is reported in the registry record. The planning figures are illustrations based on the observed effect and stated assumptions, not the original trial design rationale. Safety listings include no serious adverse events in either group, one other adverse event in the fed group, and death counts that are not reported.