Long-term Active Surveillance Study for Oral Contraceptives (LASS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Long-term Active Surveillance Study for Oral Contraceptives (LASS) (NCT00676065), a registered phase not stated study. The primary outcome is Arterial Thromboembolism.

2. Clinical Question

In statistical terms, the intended comparison concerns the occurrence of a clinically defined event across groups with different contraceptive exposures. Because treatment assignment was not randomized, the groups may differ in ways that also relate to outcome risk. The study can therefore describe observed event patterns, but a causal interpretation would require appropriate design and analysis details. Those details and comparative outcome results are not reported in the registry record.

3. Trial Design

The Long-term Active Surveillance Study for Oral Contraceptives (LASS), registered as NCT00676065, is recorded as completed. Its start is listed as 2001-02 and its primary completion as 2011-03. The sponsor is the Center for Epidemiology and Health Research, Germany. The study objective was to characterize and compare risks associated with long-term use of drospirenone-containing oral contraceptives and other established oral contraceptives.

The registry describes three exposure groups: women taking oral contraceptives containing drospirenone, women taking products containing levonorgestrel, and women taking products containing other progestogens. The record explicitly indicates that this was not a randomized comparison and that allocation was not stated. The groups should therefore not be read as randomized treatment and control arms. The characteristics of the participants and the reasons for using particular products are not reported in the registry record.

Enrollment was 58303. The primary outcome description refers to the ITT study population, while also noting that women could stop oral contraception during the study. It says woman-years of exposure for each group are provided in addition. This distinction matters: a count of participants and accumulated exposure time answer different descriptive questions, especially when exposure may change during follow-up. The actual group-specific woman-year values are not reported in the registry record used for this analysis.

The record lists three outcome measures and six analyses. It identifies arterial thromboembolism as the primary outcome, with a timeframe of within 10 years. Further outcome definitions, analysis methods, and comparative estimates are not reported in the registry record. The completion status and dates describe the study's registry milestones; they do not by themselves establish which analyses were conducted or what results were obtained.

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: The number of participants refers to the ITT study population. During the course od the study, women could for example stop use of oral contraception at any point of time. Therefore, the woman-years of exposure for each group are provided in addition.

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 Arterial Thromboembolism, measured over Within 10 years.

The primary endpoint is the number of participants with arterial thromboembolism within 10 years. The registry describes the outcome as arterial thromboembolism associated with use of oral contraceptives containing drospirenone, levonorgestrel, or other progestogens. It specifies participants as the unit and identifies the measure as a number of participants with an event.

A binary endpoint records whether each participant experienced the specified event during the defined period. Summing those participant outcomes gives a count, but a count alone is not a risk estimate or a comparison between groups. Interpreting group differences also requires the relevant denominators, a clear definition of follow-up, and an analysis that accounts for exposure and time at risk. The record notes that women could stop oral contraception and that woman-years of exposure are relevant, underscoring why participant counts and exposure time should not be conflated.

Arterial thromboembolism is the primary endpoint because it is the outcome named as primary in the registry record and is central to the stated objective of comparing risks. The registry record does not report the outcome counts by group, comparative estimates, or uncertainty intervals. Thus, the endpoint's definition is available, but the posted information does not establish the observed magnitude or precision of any group comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a binary participant outcome: whether a participant had arterial thromboembolism within 10 years. General statistical methods for binary outcomes can summarize event counts, proportions, or comparisons between proportions. The registry record does not report the group-specific primary event counts or which statistical model or test was used, so no particular method should be attributed to the study.

What does a participant count tell us?

A count states how many participants experienced an event. By itself, it does not indicate how common the event was within a group unless the corresponding denominator is also known and appropriate. A proportion uses the number of participants with an event relative to a defined participant group. A rate instead relates events to accumulated time at risk. These measures answer related but distinct questions and are not interchangeable.

The registry notes that women could stop oral contraception during the study and says that woman-years of exposure for each group are provided in addition to the ITT participant population. General methods for rates use this accumulated time to describe event occurrence in relation to exposure and follow-up. The group-specific exposure values and the primary outcome results are not reported in the registry record, so an exposure-adjusted comparison cannot be reconstructed from the information listed.

Why does the nonrandomized comparison matter?

In a randomized study, assignment is designed to balance measured and unmeasured characteristics across groups on average. This record says the comparison was not randomized and that allocation was not stated. In general, observational exposure groups can differ in participant characteristics, clinical circumstances, or other factors related to the outcome. A statistical adjustment can address measured differences only when relevant information is collected and an appropriate model is specified; it cannot guarantee removal of unmeasured confounding.

The registry record does not report the covariates used in any adjustment, the model form, diagnostic checks, or sensitivity analyses. It is therefore not possible to assess whether the posted analyses controlled for particular differences between groups. The group labels identify contraceptive exposures, but they do not establish that the groups were comparable in all other respects.

How should uncertainty be interpreted?

In general, a confidence interval expresses uncertainty around an estimated effect under the chosen statistical model and its assumptions. A narrow interval indicates greater statistical precision than a wide interval, but neither width nor statistical significance can correct a biased comparison. A p-value, in general, measures how surprising data at least as extreme as those observed would be under a specified null model; it is not the probability that the null hypothesis is true. No primary-outcome confidence intervals or p-values are reported in the registry record.

Event counts can be small for uncommon outcomes even in a large enrolled population. General statistical methods must then account for the information actually available for the endpoint, rather than treating total enrollment as though every participant had an observed event or complete follow-up. The record does not state the primary event counts, missing-outcome handling, or numbers analyzed by group. Thus, the precision of the primary comparison cannot be assessed.

What role does over-dispersion play?

Over-dispersion is a general concern in count models when observed variability exceeds what a model's distribution assumes. It can make standard errors too small if ignored, creating an appearance of greater precision than the data support. This concept is relevant to some count-data analyses, but the registry identifies the primary measure as participants with an event and does not report a count model or any over-dispersion assessment. No claim can be made that over-dispersion was present or that a particular remedy was used.

What can be inferred from the analysis listing?

The record lists three outcome measures and six analyses, but does not report the full set of analyses or how each was conducted. General statistical practice distinguishes prespecified primary analyses from secondary or exploratory analyses, and may address the increased chance of false-positive findings when many comparisons are made. The registry record does not report an analysis plan, a multiplicity adjustment, or which analyses correspond to each outcome. It is not possible to infer the plan from the number of listed analyses alone.

The sample-size assumptions described for planning illustrations are not the study's own design justification. In general, such illustrations can show how sample size depends on a chosen effect, significance level, allocation, and modeling assumptions. They do not demonstrate that the study had a particular probability of detecting an effect, nor are they observed results. The registry record does not report the trial's own sample-size justification.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("DRSP/EE", "OC-LNG", "OC-other")
n      <- c(16534, 15428, 26341)
events <- c(7, 22, 34)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  DRSP/EE  16534  7  0.0  0.0  0.1  0.0  0.1  0.0  0.1
ARM  OC-LNG  15428  22  0.1  0.1  0.2  0.1  0.2  0.1  0.2
ARM  OC-other  26341  34  0.1  0.1  0.2  0.1  0.2  0.1  0.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and six analyses. Those counts alone do not identify which analyses were primary, which were secondary, whether they involved distinct outcomes or subgroups, or whether an adjustment for multiple testing was used. The multiplicity strategy is not reported in the registry record. In general, testing multiple hypotheses can increase the chance of at least one false-positive result if each is assessed without regard to the others. Adjustment methods and prespecified analysis hierarchies can help manage that issue, but the record does not describe their use.

The primary outcome description refers to the ITT study population and notes that women could stop oral contraception during the study. This establishes that discontinuation was possible, but it does not explain how exposure changes were handled in analysis or how the ITT population was operationalized. The record also says woman-years of exposure for each group are provided in addition, but the values are not reported in the registry record used.

Missing outcome data, losses to follow-up, exclusions, and the handling of incomplete records are not reported in the registry record. It also does not state how many participants were included in each primary analysis or whether any imputation or other missing-data method was used. In general, missingness can affect both the estimated event frequency and the comparability of groups, particularly if the chance of missing data is related to exposure or outcome. Without these details, the possible effect of missing information cannot be assessed.

The registry's use of the term ITT should be read alongside the explicit note that participants could stop oral contraception. The record does not provide enough analysis detail to establish how that population definition relates to changes in exposure over time. No conclusions about adherence, censoring, or missing-data assumptions can be drawn from the population label alone.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: injury, poisoning, accidents, etc. (2.5%), genitourinary system (2.2%), digestive system (1.9%), cardiovascular system (1.6%), muscoskeletal system & connective tissue (1.5%).

The registry lists serious adverse-event information for three groups: DRSP/EE, OC-LNG, and OC-other. For DRSP/EE, the listed number at risk is 16534 and the number affected is 1912. For OC-LNG, those figures are 15428 and 2121. For OC-other, they are 26341 and 3936. These are safety figures, separate from the primary arterial thromboembolism outcome, and should not be treated as its event counts.

The registry also lists other-event figures. The number at risk is 16534 for DRSP/EE, 15428 for OC-LNG, and 26341 for OC-other; the number affected is recorded as 0 for each group. The registry record does not explain the precise event coding or whether these entries represent unique participants, event episodes, or another counting convention. The figures should therefore be read as the registry's reported counts, not reinterpreted as rates.

Serious-event categories listed include Injury, poisoning, accidents, etc. at 2.5%, Genitourinary system at 2.2%, Digestive system at 1.9%, Cardiovascular system at 1.6%, Muscoskeletal system & connective tissue at 1.5%, and Psychiatric & neurological disorders at 1.0%. The denominator used for these percentages is not reported in the registry record. Death counts are also not reported in the registry record. These entries do not establish comparative risk or causation.

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

The registry record establishes that LASS was a completed active surveillance study intended to characterize and compare risks associated with long-term use of drospirenone-containing oral contraceptives and other established oral contraceptives. It identifies three exposure groups, an enrollment of 58303, and arterial thromboembolism within 10 years as the primary outcome. These are useful details for understanding the study question and its scope.

The record does not report the primary event counts by group, the comparative estimates, or measures of uncertainty. As a result, the posted information does not show whether observed arterial thromboembolism outcomes differed among the exposure groups, how large any difference was, or how precisely it was estimated. The study objective must not be mistaken for a result, and the safety counts are not a substitute for the missing primary-outcome comparison.

The comparison is not randomized, and allocation is not stated. In general, observational comparisons can be affected by differences between groups that are also related to outcomes. The registry record does not describe adjustment methods or other steps used to address such differences. Even a reported association would therefore need interpretation in light of the design and analysis assumptions; the available record does not permit that evaluation.

The record notes that women could stop using oral contraception and that woman-years of exposure are relevant, but does not report the exposure values in the material analyzed. It also does not report how missing outcome information was handled or how the six listed analyses relate to the three outcomes. Those omissions limit assessment of follow-up, analysis populations, and multiplicity.

In short, the available information supports describing the study's purpose, population structure, endpoint definition, and selected safety listings. It does not support a conclusion that one contraceptive group had higher or lower arterial thromboembolism risk, nor a conclusion about the clinical importance of any comparison.

14. Why This Trial Matters Statistically

This study is statistically notable because it asks a long-term safety question in an active surveillance setting rather than a randomized comparison. That setting can include a large enrolled population and multiple real-world exposure groups, but group membership is not assigned at random. General statistical interpretation must therefore consider confounding and differences in follow-up, not only the number of participants enrolled.

The registry's note that participants could stop oral contraception highlights a key distinction between membership in a study population and continued exposure to a product. Participant-based summaries and exposure-time summaries answer different questions. Reporting woman-years alongside participant counts can be important when exposure changes during observation, although the specific exposure values are not reported in the registry record used.

The record also illustrates why outcome definitions and results must be distinguished. It specifies arterial thromboembolism within 10 years as the primary endpoint and gives the intended comparison, but does not report the comparative estimates. A clearly stated endpoint alone cannot establish the direction or precision of a finding. Event counts, denominators, effect estimates, and uncertainty measures are all relevant to a statistical interpretation.

The safety listings add another reason for careful reading: serious adverse-event counts and event-category percentages are not interchangeable with the primary outcome. Their denominators and counting conventions are not fully described in the registry record, and they cannot be used to infer the missing primary comparison.

More broadly, the record demonstrates the limits of interpreting a registry entry without a full analysis description. It lists outcomes and analyses, but not the multiplicity strategy, missing-data methods, adjustment variables, or primary comparative results. Statistical transparency matters because those details determine what an estimate means and how much confidence readers can place in its precision and interpretation.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting this record is that it does not report group-specific arterial thromboembolism counts or comparative estimates. No direction, magnitude, or precision of the primary comparison can be assessed. The registry does state that the primary endpoint is a participant count within 10 years, but the results needed to interpret that endpoint are absent from the information listed.

The comparison was not randomized, and allocation is not stated. The registry record does not describe participant characteristics across groups, prescribing factors, adjustment variables, or methods to address confounding. This prevents assessment of whether observed group differences, if any, could be separated from differences in the participants or circumstances associated with each exposure.

Exposure and follow-up details are also limited. The record says women could stop oral contraception and that woman-years of exposure for each group are provided in addition, but the group-specific values are not reported in the registry record used. The handling of exposure changes, censoring, and incomplete follow-up is not described. Missing outcome data and the number analyzed by group are also not reported.

Although three outcomes and six analyses are listed, the record does not identify their full relationship or state whether multiplicity was addressed. It does not report the statistical methods, analysis plan, sample-size justification, or sensitivity analyses. The adverse-event listing includes serious-event counts and category percentages, but the denominator for the category percentages and the counting conventions are not reported. Death counts are not reported in the registry record.

These limitations do not establish that the study analyses were inadequate; they define what cannot be evaluated from the registry information available. A fuller assessment would require the comparative outcome results and the methods used to produce and interpret them.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Long-term Active Surveillance Study for Oral Contraceptives (LASS) — NCT00676065.
• Registry record last updated 2014-11-19; status last verified 2014-11.
• Results first posted 2014-11-19.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT00676065, the Long-term Active Surveillance Study for Oral Contraceptives (LASS), is recorded as completed. The study began in 2001-02, reached primary completion in 2011-03, and enrolled 58303 participants. Its objective was to characterize and compare risks associated with long-term use of drospirenone-containing oral contraceptives and other established oral contraceptives.

The registry describes groups using drospirenone, levonorgestrel, or other progestogens. It identifies arterial thromboembolism within 10 years as the primary endpoint and notes that participants could stop oral contraception during follow-up. The comparison was not randomized, and allocation was not stated.

Serious adverse-event counts and selected event categories are listed, but comparative primary outcome estimates, uncertainty measures, and key analysis details are not reported in the registry record. The available information therefore describes the study question and some safety data without establishing the direction or precision of the primary comparison.