CYP2D6 Polymorphism in Patients of General Practice in Austria: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CYP2D6 Polymorphism in Patients of General Practice in Austria (NCT03859622), a registered phase not stated study. The primary outcome is Frequency of Metabolizer Status (PM, IM, NM, UM) in Patients.

2. Clinical Question

The primary question is descriptive: it concerns how many participants fall into each genetically determined metabolizer category. The registry explains that status is derived from a participant’s CYP2D6 alleles and genotype. It does not frame the primary endpoint as a comparison of treatments, nor does it identify a treatment effect to estimate.

The study also has prescribing-context aims. It describes extracting electronic records covering the last 3 years to assess patients receiving one or more drugs metabolized by CYP2D6. The registry lists secondary outcomes about whether the family physician considered prior knowledge of metabolizer status important before prescribing a CYP2D6-specific drug, and about the number of practice patients whose records were assessed.

The category frequencies are not reported in the registry record. Therefore, the clinical question can be identified, but its answer cannot be quantified from the reported results. The record also does not establish whether the observed status distribution represents patients outside this single practice.

3. Trial Design

This is an observational, cross-sectional cohort study in general practice in Austria. The registry names one observational cohort and describes patients visiting a practice for a routine blood test. It does not describe random assignment, an assigned treatment, or a concurrent control group. Allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison.

The primary endpoint concerns the frequency of CYP2D6 metabolizer status among patients with a prescription for a CYP2D6-relevant drug during the last 3 years. The registry describes the relevant categories as poor, intermediate, normal, and ultra-rapid metabolizer status. It states that status is genetically determined from the combination of two CYP2D6 alleles, through the participant’s genotype.

The record also describes a practice-record review: electronic health records for the last 3 years were to be assessed for patients receiving one or more CYP2D6-metabolized drugs. In addition, consecutive patients with unknown CYP2D6 status who attended for a routine blood test were tested if they were taking a relevant drug. These elements provide prescribing and patient context, but the registry does not report detailed results for them.

The registry lists enrollment of 289 and marks the study completed. The recorded study start is 2017-10-09, and primary completion is recorded as 2018-10-09. The primary-outcome description notes that two patients’ metabolizer status could not be determined because of technical problems. It does not give category-specific counts or explain further how those cases were handled in analyses.

The sponsor is Karl Landsteiner Institute for Systematics in General Medicine. The registry record does not report a prospective statistical analysis plan, a sample-size justification, or details about recruitment beyond the consecutive-patient description. Those omissions limit what can be inferred about the intended analysis and the representativeness of the enrolled patients.

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

Analysis population for the primary outcome, as defined in the registry: 289 unselected consecutive patients with a prescription of a CYP2D6 relevant drug during the last 3 years and who are visiting the practice office for a routine blood test. Due to technical problems the metabolizer status of two patients could not be determined!

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 Frequency of Metabolizer Status (PM, IM, NM, UM) in Patients, measured over 1 Year.

The primary endpoint is the frequency of metabolizer status among participants, with status classified as poor, intermediate, normal, or ultra-rapid. Its unit is participants, and the registry describes the measure as a count of participants. The timeframe is listed as 1 Year.

The endpoint is used to describe the distribution of genetically determined CYP2D6 categories in the study population. As a descriptive measure, it can show how often each category occurs among the participants whose status is determined. It does not, by itself, compare treatment outcomes or establish that a metabolizer category caused a particular clinical event.

The registry explains that each participant has two individual CYP2D6 alleles; their combination defines a genotype, from which metabolizer status is derived. The primary-outcome population is described as 289 unselected consecutive patients prescribed a CYP2D6-relevant drug during the last 3 years and visiting for a routine blood test. The record notes technical problems prevented status determination for two patients.

Category-specific participant counts are not reported in the registry record. Without those counts, the observed frequency of each status cannot be interpreted or compared across categories. The record also does not describe how the four categories were measured beyond the genetic classification process.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a count-based primary outcome: participants are classified by CYP2D6 metabolizer status. The categories are poor, intermediate, normal, and ultra-rapid. The method is descriptive in aim, rather than a randomized treatment-effect comparison. The category counts themselves are not reported in the registry record, so no numerical estimate of the distribution or its precision can be discussed.

What does a count-based endpoint show?

In general, a count reports how many observations fall into a defined category. For a categorical endpoint, readers need the count in each category and a clear denominator to understand the distribution. A count alone does not establish a causal relationship, and category counts should not be treated as interchangeable with treatment effects. In this study, the registry specifies participant counts as the endpoint unit but does not report the category-specific results.

The record says metabolizer status is derived from the combination of a participant’s two CYP2D6 alleles, through genotype. This describes the classification logic at a high level. Details such as the laboratory procedure, genotype-calling rules, quality-control thresholds, and handling of ambiguous results are not reported in the registry record. The two cases with undetermined status are attributed to technical problems, but the nature of those problems is not stated.

Why do denominators and missing outcomes matter?

In general, a frequency is interpretable only when its denominator is clear. Enrollment describes the number entering or registered in a study, whereas an endpoint denominator reflects participants with usable outcome information under the analysis definition. Those quantities need not be identical when outcomes are missing. Here, the registry describes 289 patients and says two statuses could not be determined; it does not report the analyzed denominator or category counts. It would therefore be inappropriate to derive category frequencies from the enrollment figure.

Missing outcome information can affect descriptive estimates if the participants without results differ systematically from those with results. In general, a missing-data assessment can describe the extent and reasons for missingness and examine whether conclusions change under reasonable assumptions. The registry record does not report such an assessment or a sensitivity analysis. The technical explanation is recorded, but it does not establish whether the missing status information is unrelated to the status distribution.

What can be inferred from the design?

In general, an observational study records exposures or characteristics without assigning participants to treatment groups. A cross-sectional description can characterize the observed population at the period of assessment, but it does not by itself establish temporal or causal effects. This study is described as observational and cross-sectional, with no like-for-like control comparison. The registry does not state an allocation scheme or describe an assigned intervention.

Because the study is based in a single general practice, its observed distribution would directly characterize the enrolled population rather than automatically represent all patients in Austria or all people taking CYP2D6-relevant drugs. In general, broader generalization depends on how participants were selected, the setting, and similarities between the study population and the population of interest. The record says patients were consecutive and unselected within the stated practice context, but it does not report enough detail to assess representativeness beyond that context.

How should uncertainty and significance be read?

In general, a confidence interval expresses the range of estimates compatible with the data under a specified statistical method. Its width reflects statistical precision as well as the amount and variability of information. A p-value addresses compatibility with a specified null model; it is not a measure of clinical importance or proof of causation. Neither confidence intervals nor p-values for the primary endpoint are reported in the registry record, so the uncertainty and statistical significance of the category frequencies cannot be assessed.

The registry lists one analysis, but does not describe the analysis method, confidence level, model, or inferential objective. A registered count outcome does not identify by itself whether the investigators used descriptive summaries, hypothesis tests, or a particular adjustment strategy. Those details are not reported in the registry record.

What do planning illustrations mean?

In general, a sample-size planning illustration asks how much information a future study might need for a stated statistical objective under chosen assumptions. The assumptions recorded for the illustration include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. The record specifies participants per arm for most outcomes and a total event count for time-to-event outcomes. Such planning values are illustrative, not observed power and not evidence that the study was designed with those assumptions. The registry does not report the study’s own sample-size justification.

For this study’s descriptive primary question, the key missing information is the status frequency data and their uncertainty. Without those results, statistical interpretation cannot move from the registered question to a quantified finding.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures, including the primary metabolizer-status frequency and secondary outcomes concerning the physician’s view of prior status knowledge and the number of practice records assessed. It lists one analysis. The registry record does not report a statistical analysis plan specifying which outcomes were tested together, the order of analyses, or whether any multiplicity adjustment was used.

In general, when several hypotheses are tested, the chance of at least one apparently unusual result can increase if each test is interpreted independently. An analysis plan can address this by identifying primary and secondary questions in advance and specifying whether and how inference is adjusted. The presence of several registered outcomes alone does not establish that multiple significance tests were conducted. No p-values or inferential results for the registered outcomes are reported in the registry record.

The primary outcome description reports technical problems that prevented status determination for two participants. The registry does not state how those cases were handled in the analysis, whether any other primary-outcome data were missing, or whether sensitivity analyses were performed. The primary endpoint counts and analysis denominator are not reported in the registry record. Therefore, a complete-case denominator or a missing-data assumption cannot be identified from the record.

The analysis population is also not described beyond the registered population wording. The record does not state whether all enrolled participants were included in each outcome analysis or whether exclusions were made. No imputation method, per-protocol population, or other analysis population is reported in the registry 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’s adverse-event fields list 289 participants at risk for serious adverse events and 289 at risk for other adverse events. Each field records zero affected participants, and deaths are recorded as zero. No serious adverse-event terms are listed.

These entries should be read as registry-recorded counts, not as proof that no adverse event of any kind occurred. The record does not describe the safety-collection process, the period of active monitoring, event definitions, or how events were attributed. It also does not explain whether the fields reflect systematic surveillance or another reporting approach. Those details are not reported in the registry record.

The study is observational, and no randomized treatment comparison is described. Accordingly, the adverse-event fields do not provide a comparative estimate of safety between interventions. The zeros are limited to the recorded fields and cannot establish the absence of unreported events or broader safety outcomes.

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

The study asks a descriptive question about CYP2D6 metabolizer status among patients in a general-practice setting who were taking a relevant drug and attended for a routine blood test. Its design and population description make the intended scope understandable. The primary endpoint is the count of participants in each status category.

The principal limitation for interpreting the finding is that the category counts are not reported in the registry record. Without those results, readers cannot determine the observed distribution, compare how common the categories were, or assess the precision of the estimates. The record notes two technically undetermined statuses, but does not describe the analysis denominator or how those cases were treated.

The registered outcome concerns genetic classification, not whether a treatment was beneficial or harmful. The registry’s background describes how CYP2D6 can metabolize drugs and why metabolizer status may be relevant to prescribing, but the primary endpoint does not test a treatment strategy or measure patient outcomes. The study therefore cannot, on the reported primary endpoint alone, establish that using status information changes prescribing or clinical outcomes.

Because the study is observational and conducted in one Austrian general practice, any distribution would describe the enrolled patients in that setting. The registry does not establish that the findings generalize to other practices or populations. The record also does not report an analysis comparing metabolizer groups on clinical outcomes.

The reported safety fields record zero affected participants and zero deaths, but the registry does not detail the event-collection methods. These entries should not be taken as comprehensive evidence about all possible harms. In sum, the record identifies a relevant descriptive research question, while the absence of primary category counts prevents a quantitative conclusion about its answer.

13. Why This Trial Matters Statistically

Statistically, this study illustrates the difference between a well-defined descriptive question and a reported estimate. The registry identifies a population, a genetic classification, and a count-based endpoint. Yet without the category counts, the central descriptive result cannot be evaluated. A study’s aim and endpoint definition are important, but they do not substitute for the estimates needed to answer the question.

The record also makes missing outcome information consequential. It notes two technically undetermined metabolizer statuses, but does not report how those cases were handled or the denominator used for analysis. Clear reporting of both the observed counts and the analysis population is necessary to interpret a frequency estimate. Without those details, readers cannot distinguish the enrolled population from the participants contributing to a particular endpoint.

The observational design matters as well. A frequency study can characterize the recorded population, but it is not a randomized comparison and does not by itself support causal conclusions about prescribing or patient outcomes. The distinction is especially important because the registry background discusses potential relevance of CYP2D6 metabolism to drugs; the primary endpoint remains status frequency, not the effect of testing or treatment.

Finally, the registry lists several outcomes but does not report the analysis plan or multiplicity handling. Those details affect how inferential claims should be interpreted when multiple questions are examined. This record therefore highlights the value of complete outcome reporting: category counts, denominators, uncertainty, handling of missing information, and analysis methods are all needed to move from a registered question to a statistically interpretable result.

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 primary limitation is that category-specific results for the metabolizer-status endpoint are not reported in the registry record. Consequently, the main descriptive question cannot be answered quantitatively, and no estimate of precision can be assessed.

The primary-outcome description reports technical problems preventing status determination for two patients. The record does not explain the technical issue, specify how those cases were handled, provide the analysis denominator, or report whether any other outcome data were missing. It also does not report a missing-data assessment.

The study concerns patients from a single Austrian general practice who met the stated drug-prescription and routine-blood-test context. Even if outcome frequencies were reported, the registry does not provide information sufficient to establish how well this group represents patients in other settings. The consecutive, unselected description applies within the practice context and does not resolve broader generalizability.

The study is observational and does not describe a like-for-like control group. Its primary endpoint is a genetic status frequency, not a treatment comparison or patient outcome. It therefore cannot establish a causal effect of knowing metabolizer status or of changing prescribing. The registry also does not report laboratory procedures or detailed status-classification rules beyond the allele-to-genotype-to-status description.

Finally, the registry lists five outcome measures and one analysis but does not report the statistical analysis plan, inferential methods, multiplicity handling, confidence intervals, or sample-size justification for the study. These omissions constrain assessment of the intended analysis and the strength of any statistical conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: CYP2D6 Polymorphism in Patients of General Practice in Austria — NCT03859622.
• Registry record last updated 2019-10-30; status last verified 2019-10.
• Results first posted 2019-10-30.
• 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

The registry record describes NCT03859622, titled CYP2D6 Polymorphism in Patients of General Practice in Austria. It is an observational, cross-sectional study sponsored by Karl Landsteiner Institute for Systematics in General Medicine and marked completed. The recorded study start is 2017-10-09, primary completion is 2018-10-09, and enrollment is 289.

The primary endpoint is the frequency of poor, intermediate, normal, and ultra-rapid CYP2D6 metabolizer status among patients prescribed a relevant drug and attending for a routine blood test. The registry notes that two statuses could not be determined because of technical problems. Category-specific primary results are not reported in the registry record.

The registry lists five outcome measures and one analysis. It also records zero affected participants in the serious and other adverse-event fields and zero deaths. The record does not report a statistical analysis plan, sample-size justification, or detailed methods for handling missing status results.