This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Use of Oral Contraceptives (OCs) Containing Dienogest and Risk of Venous Thromboembolism (NCT00523614), a registered phase not stated study. The primary outcome is Risk of Venous Thromboembolism (VTE) Between Women Who Use Dienogest/Ethinylestradiol (DNG/EE) and Women Who Use Other Low-dose Combined Oral Contraceptives (COC).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00523614 |
| Phase | Phase not stated |
| Condition | Venous Thromboembolism |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 3400 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Center for Epidemiology and Health Research, Germany |
| Results posted | Yes |
2. Clinical Question
The study concerns whether venous thromboembolism (VTE) risk differs between women using dienogest/ethinylestradiol (DNG/EE) and women using other low-dose combined oral contraceptives (COCs). The brief description also frames the objective as comparing oral contraceptive use with non-use, with particular attention to Valette® relative to other users of low-estrogen-dose combined oral contraceptives. These descriptions are related but not identical: the stated primary outcome names a comparison between DNG/EE users and users of other low-dose COCs.
VTE includes deep venous thrombosis and pulmonary embolism. The record says diagnoses in the cases group were established using imaging methods. It labels the two groups “Cases” and “Controls,” rather than identifying a randomized treatment and control arm. Allocation is not stated, and the registry specifically flags that this is not a randomized comparison and that the arms are not a like-for-like control comparison. The group labels therefore matter when interpreting the recorded counts.
The registry lists an enrollment of 3400 and describes 680 cases and 2720 controls in the adverse-event information. Those figures do not provide the missing primary outcome comparison. The primary outcome is specified as a number of participants, but the registry record does not report the outcome counts by contraceptive exposure, an effect estimate, or uncertainty around an estimate. It is therefore possible to describe the research question and design labels, but not to determine from the record how large or precise any observed association was.
Population
Women in a study of VTE, with cases diagnosed during 01/2002 - 01/2008. Further eligibility criteria and the characteristics of the analyzed population are not reported in the registry record.
Intervention
The exposure of interest is use of DNG/EE, with the brief description specifically naming Valette®.
Comparator
The primary outcome names women using other low-dose COCs. The brief description also mentions non-use, but the registry record does not give a separate primary comparison result for non-users.
Primary question
How does the recorded VTE participant count compare between DNG/EE users and users of other low-dose COCs?
3. Trial Design
The registry identifies this as a completed study of VTE and oral contraceptive use, sponsored by the Center for Epidemiology and Health Research, Germany. The listed start is 2007-07. The stated timeframe for the primary outcome is 01/2002 - 01/2008, described as the period when VTE was diagnosed in the cases group. The registry lists enrollment of 3400. It labels the groups “Cases” and “Controls,” and does not provide descriptive details for the arm descriptions.
The design is not reported as a randomized comparison. The registry explicitly notes that allocation is not stated and that the arms are not a like-for-like control comparison. The labels indicate a case-control structure, but further details about how cases and controls were identified, selected, matched, or sampled are not reported in the registry record. The record also does not describe how contraceptive exposure was measured, the reference period for exposure, or how potential confounding factors were handled.
These omissions affect what can be interpreted. In general, case-control studies begin with groups defined by outcome status and compare prior exposures; the precise interpretation depends on how participants were selected and how exposure information was collected. A count of cases and controls alone does not establish the underlying risk in each exposure group. The registered primary outcome title refers to “risk,” while its parameter is a participant number. Without the exposure-specific outcome data and the analytic method, the record does not show how the investigators translated those counts into a risk comparison.
The registry lists one outcome measure and one analysis. It does not report the statistical analysis plan, adjustment variables, or details of the analysis population. Nor does it provide information about recruitment locations, follow-up procedures, or the handling of participants with incomplete information. The available design description supports identifying the study as an observational, non-randomized comparison of cases and controls, but not reconstructing the full conduct of the study.
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
| Stage | Cases | Controls |
|---|---|---|
| STARTED | 680 | 2720 |
| COMPLETED | 680 | 2720 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | Cases | Controls | Total |
|---|---|---|---|---|
| Participants analysed | 680 | 2720 | 3400 | |
| Age, Categorical: <=18 years | Participants | 15 | 60 | 75 |
| Age, Categorical: Between 18 and 65 years | Participants | 665 | 2660 | 3325 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age Continuous | years | 36.1 (SD 9.0) | 36.1 (SD 9.0) | 36.1 (SD 9.0) |
| Sex: Female, Male: Female | Participants | 680 | 2720 | 3400 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Region of Enrollment: Germany | participants | 680 | 2720 | 3400 |
6. Primary Endpoint
The registry lists the primary outcome as Risk of Venous Thromboembolism (VTE) Between Women Who Use Dienogest/Ethinylestradiol (DNG/EE) and Women Who Use Other Low-dose Combined Oral Contraceptives (COC), measured over 01/2002 - 01/2008.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is titled as the risk of VTE among women using DNG/EE compared with women using other low-dose COCs. Its unit is participants and its parameter is a number. The outcome description defines VTE as deep venous thrombosis or pulmonary embolism and states that diagnoses in the cases group were established using magnetic resonance imaging, spiral computer tomography, duplex sonography, and lung scintigraphy. The diagnosis timeframe is 01/2002 - 01/2008.
Counting participants with an event is a direct way to describe how many people in a defined group experienced the event. It is not, by itself, a measure of comparative risk: interpreting a count requires knowing the relevant exposure groups, the denominators or sampling scheme, and how the comparison was analyzed. This is particularly important in a case-control design, where the numbers selected as cases and controls need not represent the frequency of VTE in the underlying population.
The endpoint is clinically relevant to the research question because it captures the event the study set out to examine. However, the registry record does not report the primary endpoint counts by contraceptive exposure, nor does it report a relative or absolute effect estimate or confidence interval. Thus, the endpoint definition is available, but the magnitude and precision of the exposure comparison cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the topic, outcome definition, group labels, and intended comparison. It does not provide the numerical primary results necessary to judge the direction, size, or precision of an association between DNG/EE use and VTE. Although the primary outcome is described as a number of participants, no exposure-specific VTE counts appear in the record. No risk ratio, odds ratio, risk difference, confidence interval, or primary analysis p value is reported in the registry record.
The distinction between the study's question and its result is important. A comparison can be clearly stated without the evidence needed to answer it. The brief description mentions oral contraceptive use versus non-use and focuses on Valette® relative to other low-estrogen-dose COC users. The primary outcome title instead specifies DNG/EE users versus users of other low-dose COCs. The record does not reconcile these framings or report a separate result for non-use. No conclusion about which exposure group had more or fewer VTE events can be drawn from the available primary outcome information.
The adverse-event fields list 0 serious events affected and 0 other events affected for the cases group and the controls group. These are registry adverse-event entries, not the primary VTE outcome comparison. They should not be treated as a substitute for the missing exposure-specific VTE results. The record does not explain the relationship between these event fields and the primary endpoint, and the deaths fields are not reported in the registry record.
For a quantitative interpretation, an effect estimate would need to be read together with its uncertainty. A confidence interval describes a range of values compatible with the data and analysis under its assumptions; a narrower interval generally indicates greater precision. Neither an estimate nor an interval is reported in the registry record, so the precision of the comparison cannot be assessed. The absence of a reported p value also means there is no basis in the record for describing the result as statistically significant or not statistically significant.
The study is explicitly flagged as non-randomized, with allocation not stated and the arms not identified as a like-for-like control comparison. This limits causal interpretation: exposure groups may differ in ways that also relate to VTE, and the record does not describe whether or how such differences were addressed. This is a limitation of what can be inferred from the posted information, not evidence that any specific bias occurred. The defensible interpretation is therefore narrow: the registry describes an observational question about VTE and contraceptive exposure, but it does not report the primary comparison result needed to quantify the association.
9. Statistical Methods Explained
The registry identifies the primary outcome as binary in kind and describes its meaning as participants with an event, recorded as counts. It specifies a participant number rather than a rate, time-to-event measure, or continuous measurement. This points to counting people who met the VTE definition, but the registry does not report the actual primary counts by contraceptive exposure. Nor does it specify a model or test used for the comparison.
What does a participant count tell the reader?
A count answers how many people in a defined group experienced an event. For a comparison, counts must be understood in relation to the groups being compared and the way people entered those groups. In a cohort setting, denominators and follow-up time can help describe event frequency. In a case-control setting, the number of cases and controls is often determined by selection into the study, so those group counts do not automatically estimate population risks. This is general statistical context; the specific sampling details needed to determine the appropriate interpretation are not reported in the registry record.
The registry lists cases and controls, while the primary outcome asks about contraceptive exposures within those groups. The relevant analysis would need to connect VTE status with exposure status. The record does not give the exposure-by-outcome counts, so an association measure cannot be reconstructed. It also does not report whether the analysis was adjusted or unadjusted, which variables might have been included, or how missing exposure or outcome information was handled.
How should uncertainty be read?
An effect estimate describes the size and direction of a comparison under a stated analysis. A confidence interval describes uncertainty around that estimate: it indicates which values remain compatible with the data and assumptions of the method. The interval does not repair limitations in study design or remove confounding. In this case, no primary effect estimate or confidence interval is reported in the registry record, so neither magnitude nor precision can be evaluated. No primary p value is reported either.
For observational comparisons, adjustment may be used to account for measured characteristics that differ between exposure groups and relate to the outcome. Adjustment does not automatically eliminate bias, and it cannot address factors that were not measured or modeled. The registry record does not identify any adjustment factors or state whether the reported analysis was adjusted. It is therefore not appropriate to describe the result as adjusted, unadjusted, or controlled for any particular factor.
What is the role of the planning assumptions?
The registry's planning description characterizes sample-size calculations as illustrations based on the observed effect, with two-sided significance level 0.05, equal allocation between arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not a description of the study's original design or proof that the study achieved a particular probability of detecting an effect. The record does not report a sample-size justification from the investigators, and the primary numerical effect is not reported in the registry record. Any calculated sample-size values should therefore be read as planning illustrations, not observed power or evidence that the study was adequately powered.
The planning description also distinguishes analyses of time-to-event outcomes, for which it refers to total events, from other outcomes, for which it refers to participants per arm. The primary outcome is specified as a participant count, and the registry does not identify it as a time-to-event analysis. No additional calculation of power or sample size can be justified from the primary results recorded in the registry.
Why does the design affect the method?
In general, a case-control study compares exposure distributions among people with and without the outcome. The interpretation depends on participant selection and exposure measurement. An odds ratio is commonly used for such comparisons, but the registry does not report an odds ratio or state that this was the method used. It would be inappropriate to infer an analysis method from the group labels alone. Likewise, the word “risk” in the outcome title does not establish that the analysis estimated an absolute risk.
The record lists one outcome measure and one analysis, but that count does not describe the statistical procedure, model specification, or multiplicity strategy. Without those details and without the primary results, the statistical methods cannot be independently evaluated. General statistical principles can explain what counts, intervals, adjustment, and planning calculations mean, but they cannot fill in unreported design or analysis details.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure and one analysis. This is a count of registered entries, not a full description of the analysis plan. The record does not state whether additional outcomes or analyses were conducted outside the entries shown, whether any outcome was designated as primary before analysis, or how multiple comparisons were handled. The multiplicity strategy is not reported in the registry record.
Multiplicity matters when many outcomes, subgroups, or analytic choices are examined, because the chance of a seemingly notable finding can increase across repeated tests. Statistical approaches can address that issue, but the appropriate approach depends on the planned questions and analysis. No correction method, testing hierarchy, or interim analysis plan is reported in the registry record. It is therefore not possible to assess whether multiplicity was a concern or how it was addressed.
Missing-data procedures are also not described. The record does not state how missing exposure histories, outcome information, or other covariates were handled, whether any imputation was used, or how incomplete records affected inclusion. The analysis population is not defined beyond the case and control labels and the adverse-event counts. The number of participants included in the primary outcome analysis is not reported in the registry record.
These omissions matter because the analyzed sample and treatment of missingness can influence both an estimate and its uncertainty. The registry record also does not describe exclusions, protocol deviations, or whether analysis followed a prespecified population definition. No conclusion should be drawn about the presence or absence of missing data, or the adequacy of its handling, from the absence of a description.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Cases | 0 | 680 | 0.0% |
| Controls | 0 | 2720 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Cases | 0 of 680 |
| Controls | 0 of 2720 |
The registry's adverse-event entries list 0 serious events affected and 0 other events affected for the Cases group, whose at-risk count is 680. The corresponding entries for the Controls group list 0 serious events affected and 0 other events affected, with an at-risk count of 2720. The serious-event terms list is empty. The deaths fields are not reported in the registry record.
These entries should be read as the values recorded in the adverse-event fields, not as a full account of the study's VTE findings. VTE is the primary outcome, whereas these entries appear in the registry's adverse-event information. The record does not explain how adverse-event reporting relates to the primary endpoint or whether these fields cover all events relevant to the research question. The zero entries therefore do not establish that no VTE events occurred in the study.
Counts of affected participants also do not show the severity, timing, or exposure-specific distribution of events unless those details are reported. Here, no event terms are listed, and no additional safety narrative is available. The entries should not be used to infer a comparative safety effect or to conclude that either exposure group had no risk. They are limited registry fields whose relationship to the primary outcome is unclear.
12. What the Result Does, and Does Not, Mean
The record identifies a clinically specific question: whether VTE differs between women using DNG/EE and women using other low-dose COCs. It defines VTE to include deep venous thrombosis and pulmonary embolism and describes diagnostic imaging used for cases. It also identifies the study as completed and labels the groups as cases and controls. These elements help define what the investigation concerned.
What the record does not establish is the size or direction of the exposure comparison. The primary participant counts by exposure, an effect estimate, a confidence interval, and a primary p value are not reported in the registry record. Consequently, the record cannot show whether the observed association was large or small, whether estimates were precise, or whether any result was compatible with materially different effects. It also cannot establish that one exposure caused more or fewer VTE events than another.
The non-randomized design is relevant. In general, observational exposure groups can differ in characteristics related to the outcome. A statistical adjustment can address measured differences under its assumptions, but it cannot make a non-randomized comparison equivalent to random allocation. Here the registry does not report the adjustment strategy or the characteristics used in analysis. These are uncertainties about the available record; they do not demonstrate that a particular bias affected the findings.
The adverse-event entries listing zero affected participants are not a substitute for the missing primary endpoint comparison. The record does not clarify their relation to the VTE outcome, and they should not be interpreted as evidence that VTE was absent. Similarly, the enrollment entry and the case-control counts describe study size or group structure, not the exposure-specific result.
The most supportable conclusion is about the scope of the registered question rather than its answer: the study was intended to examine VTE in relation to contraceptive exposure, but the posted record lacks the numerical primary results needed to quantify that relationship. Any conclusion about comparative risk, statistical significance, or clinical importance would go beyond what the registry record reports.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of why a clearly named outcome and comparison do not by themselves make results interpretable. The record identifies VTE, the exposure contrast in the primary outcome title, and a case-control structure. Yet the primary outcome is recorded as a participant count without exposure-specific results or a reported estimate of association. A reader can understand the question but cannot evaluate its answer from the registry record.
The mismatch between the word “risk” in the outcome title and a count-based endpoint is worth attention. A count can contribute to a risk analysis, but it must be interpreted with information about group membership, denominators, sampling, and the analysis method. In a case-control design, the selected case and control counts do not necessarily represent population frequencies. This general principle is especially relevant because the registry says allocation is not stated and warns that the arms are not a like-for-like control comparison.
The record also illustrates the value of separating primary efficacy or outcome results from adverse-event reporting fields. Zero values in adverse-event fields do not answer the primary VTE comparison when the record does not explain their relationship to that endpoint. Distinct fields can serve distinct purposes, and their labels should not be treated as interchangeable evidence.
Finally, statistical precision and design limitations are separate questions. Even a precise estimate could remain vulnerable to confounding in an observational study; conversely, a well-framed question cannot be judged without an estimate and its uncertainty. Since neither is reported, the central statistical lesson is restraint: distinguish what the study set out to compare from what the registry record permits readers to conclude.
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 for interpretation is that the registry record does not report the exposure-specific VTE counts or an effect estimate. The stated outcome is a participant number, but the counts needed to compare DNG/EE users with users of other low-dose COCs are absent. No confidence interval or p value is reported, leaving both the magnitude and precision of the association unknown.
The design description is also limited. The groups are called cases and controls, while allocation is not stated and the registry flags that the arms are not a like-for-like control comparison. How cases and controls were sampled, whether they were matched, and how exposure was assessed are not reported in the registry record. These details are important for evaluating selection and measurement bias. Potential confounding factors and any adjustment strategy are likewise not described.
The research question is framed in more than one way. The brief summary refers to oral contraceptive use with non-use and emphasizes Valette® relative to other low-estrogen-dose COC users; the primary outcome title names DNG/EE compared with other low-dose COC users. The registry record does not clarify whether non-use was analyzed as a separate comparator or how the focus on Valette® relates to the registered primary contrast.
The record does not describe missing-data handling, analysis populations, multiplicity, or a prespecified statistical plan. The adverse-event entries do not resolve the missing primary outcome information, and their relationship to VTE is not explained. These are limitations of the information recorded in the registry; they do not establish that the study itself lacked procedures or analyses that were not entered in the record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Use of Oral Contraceptives (OCs) Containing Dienogest and Risk of Venous Thromboembolism — NCT00523614.
- Registry record last updated 2010-03-23; status last verified 2010-03.
- Results first posted 2009-12-02.
- 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.
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18. Record Summary
NCT00523614 is a completed study sponsored by the Center for Epidemiology and Health Research, Germany. The registry lists a start of 2007-07 and enrollment of 3400. Its subject is VTE in relation to oral contraceptive use, with the primary outcome title specifying DNG/EE compared with other low-dose COC use. The outcome includes deep venous thrombosis and pulmonary embolism, with the stated case diagnosis timeframe of 01/2002 - 01/2008.
The record labels the groups Cases and Controls and states that the comparison is not randomized, allocation is not stated, and the arms are not a like-for-like control comparison. It lists one outcome measure and one analysis. The primary outcome is expressed as a participant count, but exposure-specific counts, an effect estimate, and its uncertainty are not reported in the registry record. Adverse-event fields list zero serious and zero other events affected in each group; the record does not explain how these entries relate to the primary VTE outcome.