CES1 Carriers in the PAPI Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CES1 Carriers in the PAPI Study (NCT03188705), a na phase 4 study. The primary outcome is Changes in Platelet Function in Response to Clopidogrel.

2. Clinical Question

The outcome is based on ex vivo platelet aggregometry: platelet-rich plasma is stimulated with ADP or collagen, and maximum aggregation is recorded as a percentage. The reported change is baseline aggregation minus aggregation measured after clopidogrel treatment and before aspirin. This makes the outcome a within-participant change over time, not a direct comparison between randomized treatment groups.

The scientific question concerns a possible association between CES1 variation and platelet response. The registry record does not report numerical primary-outcome estimates or an analysis connecting genetic variants to the measured changes. Consequently, the record alone does not establish the direction or size of any association.

3. Trial Design

NCT03188705, titled “CES1 Carriers in the PAPI Study,” is listed as a Phase 4, single-group study sponsored by the University of Maryland, Baltimore. Its official title describes enrichment of CES1 carriers in the Pharmacogenomics Anti-Platelet Intervention Study. The registry lists an enrollment of 6 and a completed status. The recorded start date is 2019-10-14, and the primary completion date is 2020-01-17.

The study builds in part on preliminary results from the Pharmacogenomics Anti-Platelet Intervention study. Its stated purpose is to assess the impact of CES1 genetic variation on response to clopidogrel and dual antiplatelet therapy in healthy Amish individuals. The intervention description gives a sequence: clopidogrel treatment alone, followed by clopidogrel plus aspirin on day 8. The primary outcome, however, is defined as a change measured after clopidogrel and before aspirin.

The record lists allocation as NA and masking as none. It describes no randomized assignment or concurrent control arm. The treatment phases therefore should not be interpreted as independently assigned groups or as a randomized comparison. A before-and-after measurement can describe change during the treatment period, but by itself it cannot separate a treatment-associated change from other temporal influences.

The record identifies two outcome measures and lists no analyses. It does not report the protocol’s statistical analysis plan, a sample-size justification, interim analyses, or the analysis population. The small enrollment and absence of reported outcome estimates limit what can be learned from the registry entry about the precision or interpretation of the primary finding.

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.

Clopidogrel Treatment

Reasons for not completing this period:

Clopidogrel Plus Aspirin Treatment

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.

6. Primary Endpoint

The registry lists the primary outcome as Changes in Platelet Function in Response to Clopidogrel, measured over Measured at baseline and after 8 days of clopidogrel treatment.

The primary outcome is titled “Changes in Platelet Function in Response to Clopidogrel.” It measures the difference between baseline maximum platelet aggregation and maximum aggregation after 8 days of clopidogrel treatment, before aspirin administration. The record defines the subtraction as baseline minus post-clopidogrel aggregation, so the sign of a change depends on that stated ordering. Measurements are expressed as a percentage of maximum aggregation change.

Aggregation is measured in platelet-rich plasma after stimulation with ADP (20 ug/ml) or collagen (5 ug/ml). The aggregometer records maximum platelet aggregation as a percentage. The outcome therefore captures a laboratory measure of platelet response to each stimulus; it is not itself a clinical event or a direct measure of patient benefit.

Ex vivo platelet aggregometry is used in this study to quantify platelet function under specified laboratory conditions. A baseline-to-follow-up change can describe how the measured response differs within a participant over the treatment period. Comparing that change with CES1 variation could address the study’s pharmacogenomic question, provided that genetic groups and their estimates are reported and analyzed appropriately.

The registry record specifies a mean and standard deviation as the summary format. It does not report the numerical outcome values, the number of observations contributing to each measure, or an estimate of association with CES1 variation. Thus, the endpoint’s definition is available, but its observed magnitude and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is continuous: it is a percentage-of-maximum-aggregation change. The registry specifies a mean as the parameter and standard deviation as the dispersion measure. These are descriptive summaries. A mean describes the average measured change in the analyzed observations, while a standard deviation describes how dispersed individual measurements are around that average. Neither summary, without the underlying values and sample size for the analysis, establishes whether a pattern is precise or attributable to a treatment.

What does the change score represent?

The registry defines the change as baseline maximum aggregation minus maximum aggregation after clopidogrel but before aspirin. This is a within-participant contrast between two measurement times. The order of subtraction matters: reversing the order would reverse the sign. The outcome is recorded for responses to ADP or collagen stimulation, so interpretation should retain which stimulus the measure refers to rather than treating the laboratory readings as interchangeable.

Change scores can be useful when the research question concerns a participant’s alteration from baseline. They also inherit measurement variation from both time points. If baseline and follow-up readings are noisy, the difference can be noisy as well. A group mean may summarize the direction of average change, but its uncertainty depends on the observed data and analysis details, which are not reported in this registry record.

How should a confidence interval be understood?

In general, a confidence interval describes the uncertainty around an estimated quantity under the assumptions of the statistical method. A narrow interval indicates greater precision than a wide interval, while an interval that spans values on either side of a null or reference value may be compatible with a range of interpretations. These are general statistical principles, not results from this study: the registry record does not report a confidence interval for the primary outcome or for a CES1 association.

A p-value, in general, measures how incompatible the observed data are with a specified null model, under the assumptions used for the test. It does not measure the probability that a hypothesis is true, the clinical importance of a difference, or the probability that chance alone generated the result. No p-value or tested hypothesis for the primary outcome is reported in the registry record, and no analysis is listed.

Why does the design matter?

A single-group before-and-after design provides no randomized concurrent group to represent what would have happened over the same period without the treatment sequence. Changes could reflect treatment, time, measurement variation, or other influences. The design can describe observed change, but causal attribution requires assumptions that the registry record does not document. The absence of masking also means the record does not describe blinded assessment or treatment delivery.

The treatment sequence includes clopidogrel alone, then clopidogrel plus aspirin on day 8. The primary endpoint is specifically measured after clopidogrel and before aspirin, so the primary change is not a comparison of clopidogrel alone against dual antiplatelet therapy. The treatment description alone does not establish that an outcome was measured after the addition of aspirin.

What do planning calculations mean?

In general, sample-size planning uses assumptions about the effect to detect, variability, significance level, allocation, and statistical model. The registry record states that its planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect set as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed study results, and they are not the trial’s own design justification. The record does not report the trial’s sample-size justification.

A two-arm planning calculation does not convert this single-group study into a randomized comparison. It describes hypothetical planning under its stated assumptions. Any planning output should not be interpreted as achieved power, a finding, or evidence that the study was adequately sized. The numerical planning outputs are not reported in the registry record analyzed.

What does over-dispersion mean in general?

For count outcomes, over-dispersion means the observed variability exceeds what a simple model assumes. It can make standard errors too small if ignored and may call for a model that accounts for extra variability. This study’s primary endpoint is continuous rather than a count, and the registry record does not describe an over-dispersion assessment. This general concept does not establish that over-dispersion occurred in this study.

More broadly, interpreting an estimate requires the outcome values, the number of observations analyzed, the chosen model, and the handling of missing measurements. The registry entry does not report those details for the primary endpoint. Its mean-and-standard-deviation description identifies the intended form of summary, but cannot substitute for estimates, uncertainty measures, or a documented analysis plan.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures and describes platelet aggregation responses to ADP and collagen. It does not report a multiplicity strategy, such as an adjustment for evaluating more than one outcome or stimulus. Without a documented plan, it is not possible to determine whether any statistical testing accounted for multiple comparisons. No analyses are listed, and no primary-outcome p-values or confidence intervals are reported.

Missing-data methods are not reported in the registry record. It does not state whether all enrolled participants had each laboratory measurement, how incomplete measurements were handled, or whether any imputation was planned or used. The number of participants contributing to each primary-outcome estimate is also not reported. Enrollment of 6 should not be assumed to equal the analysis population for every endpoint.

The record does not define analysis populations, such as a population based on all enrolled participants or a subset with completed measurements. It also does not describe exclusions or the handling of participants without genetic or platelet-function data. These omissions matter because the analyzed group and missing measurements can affect both the estimated mean and its precision.

Accordingly, multiplicity, missing-data handling, and analysis-population rules cannot be evaluated from the registry record. These are reporting gaps, not evidence that a particular method was or was not used outside the record.

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.

The registry lists safety counts separately for “Clopidogrel Alone Treatment” and “Clopidogrel and Aspirin Treatment.” For each category, 5 participants are listed as at risk for serious adverse events and 5 as at risk for other adverse events. The recorded counts are 0 serious events, 0 other events, and 0 deaths in each category. No serious adverse-event terms are listed.

These are the recorded counts, not a comparison of randomized groups. The study is described as single-group, and the treatment categories reflect the treatment sequence. The record does not explain whether the same participants contribute to both categories, nor does it reconcile the listed at-risk counts with the enrollment of 6. The figures should therefore be read as category-specific registry counts, without inferring separate independent groups.

Zero recorded events does not establish that an event is impossible or that the treatments have no safety risks. In a small study, the available observation is limited; the registry record also does not provide further detail about event collection or follow-up for safety. These counts do not address the primary platelet-function outcome.

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

The record establishes that the study was designed to examine CES1 variation in relation to platelet response in healthy Amish individuals and that the primary endpoint was a laboratory change after clopidogrel, measured before aspirin. It also records a completed study with enrollment of 6. Those details describe the research question and design, not the result of the primary analysis.

Numerical primary-outcome results are not reported in the registry record. There is no reported mean change, standard deviation, confidence interval, p-value, or estimate comparing CES1 groups. As a result, the record does not show whether platelet aggregation changed in a particular direction, how large any change was, or how precisely it was estimated. It also does not report whether CES1 variation was associated with the endpoint.

Even if a within-participant change were reported, this single-group design would not by itself establish that clopidogrel caused the change. Without randomized concurrent controls, other explanations for changes over time cannot be ruled out from the design alone. The primary outcome is measured before aspirin, so it should not be interpreted as an estimate of the added effect of aspirin or as a direct comparison of clopidogrel-only and dual therapy.

The study’s laboratory measure is not a clinical outcome. A change in ex vivo aggregation does not, by itself, demonstrate a change in cardiovascular events or other clinical outcomes. The registry record does not report such clinical results.

In short, the available record supports a precise description of the endpoint and treatment sequence, but not a conclusion about the size, direction, clinical importance, or certainty of the primary result. The absence of results in the registry entry should not be read as evidence of no effect; it means the numerical result is not reported there.

13. Why This Trial Matters Statistically

This study illustrates how a pharmacogenomic question can be connected to a defined laboratory endpoint. CES1 variation is the proposed source of differences in response, and platelet aggregometry supplies a continuous measure of platelet function under specified stimuli. Defining the endpoint’s timing and subtraction order is essential: the primary change is measured after clopidogrel and before aspirin, with baseline minus follow-up as the stated calculation.

It also highlights the distinction between a biological measurement and a clinical outcome. Platelet aggregation is an ex vivo measure. It can characterize a laboratory response, but it does not by itself show what happens to clinical events. The registry’s endpoint definition therefore needs to be interpreted within its measurement context.

The design provides a useful statistical teaching example because it is a single-group sequence rather than a randomized comparison. Repeated measurements can describe within-participant change, but do not supply a concurrent counterfactual. A design’s limits shape the claims its estimates can support, independently of how interesting the biological question may be.

Finally, the record demonstrates why complete results reporting matters. Without estimates, dispersion, uncertainty intervals, analysis populations, and missing-data details, readers cannot assess the magnitude or precision of the primary response or the association with genetic variation. A stated hypothesis and a clear endpoint are not substitutes for reported results.

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 enrollment is 6, and the record does not report the number of participants with complete primary-outcome data or the number analyzed for each stimulus. The precision of any estimate cannot be assessed because numerical outcome summaries and uncertainty measures are absent. The registry also lists no analyses, so no model or inferential approach for the CES1 question can be evaluated.

The single-group design has no randomized concurrent control, and masking is listed as none. A before-and-after change cannot isolate treatment effects from other influences over time. The sequential clopidogrel and clopidogrel-plus-aspirin descriptions also do not constitute a randomized comparison. In addition, the primary measurement occurs before aspirin, limiting its relevance to the effect of the later dual-therapy phase.

The registry record does not report how CES1 carrier status was defined for analysis, how genetic groups were formed, or how many participants carried each relevant variant. It also does not give details of the statistical analysis plan, sample-size justification, interim analyses, missing-data handling, or analysis populations. These details are necessary for evaluating the intended inference and the risk of selective or incomplete reporting.

The endpoint is a laboratory measure of aggregation in response to ADP or collagen. It is not a clinical event, and the record does not report clinical outcome results. The safety categories list 5 at risk in each treatment category despite enrollment of 6, without explaining the relationship between those denominators or whether the same participants appear in both categories. These limitations constrain interpretation of both efficacy-related and safety-related information in the registry entry.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: CES1 Carriers in the PAPI Study — NCT03188705.
• Registry record last updated 2026-07-31; status last verified 2023-05.
• Results first posted 2023-06-15.
• 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

NCT03188705 is a completed Phase 4, single-group study sponsored by the University of Maryland, Baltimore. The registry lists enrollment of 6 and describes a study of CES1 variation and platelet response in healthy Amish individuals. Participants received clopidogrel alone, followed by clopidogrel plus aspirin on day 8.

The primary endpoint is the baseline-minus-post-clopidogrel change in maximum platelet aggregation before aspirin, measured after ADP or collagen stimulation. The registry specifies mean and standard deviation summaries but reports no numerical primary-outcome estimates or analyses. It does not report a multiplicity plan, missing-data methods, analysis populations, or sample-size justification.

Safety entries list zero serious events, zero other events, and zero deaths in each treatment category, with 5 participants at risk in each. The record does not explain the category denominators. The available entry describes the question and methods, but does not establish the direction, magnitude, or precision of a CES1-related platelet response.