Transatlantic Active Surveillance on Cardiovascular Safety of NuvaRing (TASC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Transatlantic Active Surveillance on Cardiovascular Safety of NuvaRing (TASC) (NCT00524771), a registered phase not stated study. The primary outcome is Number of Participants With Venous Thromboembolism (VTE).

2. Clinical Question

3. Trial Design

TASC is an active-surveillance study of cardiovascular safety in users of NuvaRing and combined oral contraceptives. The registry record describes a comparison between the two user groups and states that the study was not randomized. Allocation is not stated. Consequently, the record does not establish that the groups were formed through a common assignment process or that they were alike at the start of follow-up.

The stated enrollment is 34100. The record lists Contraception as the condition and names the Center for Epidemiology and Health Research, Germany, as sponsor. The recorded study start is 2007-09, primary completion is 2012-03, and status is COMPLETED. The study objective refers to characterizing and comparing risks associated with short- and long-term use of NuvaRing and marketed combined oral contraceptives.

The primary endpoint is venous thromboembolism associated with hormonal contraceptives containing both estrogen and progestin. Its timeframe is described as time to event analysis within 48 months. The record lists 2 outcome measures and 7 analyses, but the details and results of those analyses are not reported in the registry record. The record also does not report how follow-up was conducted, how exposure changes were handled, or how potential differences between the user groups were addressed. These omissions limit the conclusions that can be drawn from the registry entry alone.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Study participants that were not excluded due to protocol violations.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: All study participants that were not excluded due to protocol violations.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Venous Thromboembolism (VTE), measured over Time to event analysis within 48 months.

The primary endpoint is the number of participants with venous thromboembolism (VTE), measured in participants. The record describes VTE in relation to hormonal contraceptives containing both estrogen and progestin, and specifies a time-to-event analysis within 48 months. The endpoint therefore concerns whether participants experience a VTE event during the stated analysis timeframe, with timing incorporated into the planned type of analysis.

General statistical context: time-to-event methods are used when the timing of an event matters and participants may have different lengths of observation. These methods can account for incomplete follow-up, provided the analysis plan and necessary data are available. The registry record does not report the time-to-event method, the number of VTE events, an effect estimate, or a confidence interval. It is therefore not possible from this record to assess the observed VTE frequency, the comparative estimate, or its precision.

The endpoint’s population excludes participants removed for protocol violations. The registry record does not specify the violations, the number of participants excluded, or whether other analysis populations were used. Those details matter because the definition of the population determines which observations contribute to the reported endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: a clinical comparison can be described by an estimate of the difference or relative contrast between groups, together with an interval expressing uncertainty. A confidence interval shows a range of values compatible with the data under the analysis assumptions. Narrower intervals generally indicate greater precision, while wider intervals indicate greater uncertainty. The registry record does not report an estimate or confidence interval for the primary VTE endpoint, so its precision cannot be judged.

What does a time-to-event analysis add?

General statistical context: time-to-event methods use both whether an event occurred and when it occurred. They can retain information from participants whose observation ends before an event is recorded, rather than treating every such participant as if their outcome were known. This requires a defined follow-up time and assumptions about the process that ends observation. The registry record specifies a time-to-event analysis within 48 months, but does not report the method, the event-time data, how follow-up ended, or how incomplete observation was handled.

What is the role of the comparison groups?

The named groups are NuvaRing users and users of combined oral contraceptives. The record states that this was not a randomized comparison and that allocation was not stated. General statistical context: random assignment can help balance characteristics between groups, while a nonrandomized comparison may be affected by differences in who enters each group. Adjustment can address measured differences under suitable assumptions, but cannot automatically remove bias from unmeasured or poorly measured factors. The registry record does not report baseline characteristics, adjustment methods, or a model specification.

How should counts and estimates be distinguished?

The endpoint title refers to the number of participants with VTE, while its timeframe specifies a time-to-event analysis. A count is a tally of participants meeting an event definition; a time-to-event estimate also incorporates when events occur and may account for incomplete observation. The record does not give VTE counts or time-to-event estimates. The serious adverse event counts reported separately do not provide the missing VTE comparison.

What do the planning assumptions mean?

General statistical context: a sample-size calculation describes the amount of information that a design would need under stated assumptions. It is a planning exercise, not a measure of the study’s observed ability to detect an effect. The registry record describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It also states that the effect to detect is a stated fraction of the observed effect, and that time-to-event illustrations concern the total number of events while other illustrations concern participants per arm. These assumptions describe illustrations, not the trial’s own design justification. The registry record does not report a protocol sample-size justification, and the assumptions alone do not establish what the trial was designed to detect.

What can be said about statistical significance?

General statistical context: a p-value measures how compatible data are with a specified null model under the assumptions of a test; it is not the probability that a hypothesis is true or a measure of clinical importance. The registry record does not report a p-value for the primary endpoint or the test used. It also does not report an analysis plan that would explain whether the reported comparisons were prespecified or adjusted. Thus statistical significance and the robustness of any primary comparison cannot be evaluated from this registry information.

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("NuvaRing", "Combined Oral Contraceptives (COC)", "COC2")
n      <- c(16864, 16431, 13811)
events <- c(19, 26, 21)
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  NuvaRing  16864  19  0.1  0.1  0.2  0.1  0.2  0.1  0.2
ARM  Combined Oral Contraceptives (COC)  16431  26  0.2  0.1  0.2  0.1  0.2  0.1  0.2
ARM  COC2  13811  21  0.2  0.1  0.2  0.1  0.2  0.1  0.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 2 outcome measures and 7 analyses. It does not report the analysis plan, identify which analyses were prespecified, or explain how the primary endpoint relates to the other outcomes and analyses. It also does not report whether any adjustment was planned for testing multiple outcomes or comparisons. General statistical context: examining many outcomes or analyses can increase the chance of at least one apparently unusual result, so interpretation depends on which questions were planned and how multiplicity was handled. The registry entry does not provide enough detail to assess that issue.

The primary endpoint population is described as participants not excluded because of protocol violations. The record does not define those violations, report the number of exclusions, or state how missing outcome or follow-up information was handled. It does not describe an intention-to-treat population or other analysis populations. Since the comparison was not randomized and allocation is not stated, the way participants entered and remained in each analysis group is also important; those details are not reported in the registry record.

General statistical context: missing observations can affect an estimate when the likelihood of missingness is related to exposure, prognosis, or the event itself. An analysis may make assumptions or use methods to address missing data, but those choices need to be described to judge their consequences. No missing-data strategy is reported in the registry record. The absence of these details does not prove that the analyses were inadequate; it means their handling cannot be evaluated from this entry.

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: digestive system (1.0%), genitourinary system (0.8%), injury, poisening, accidents, etc (0.7%), cardiovascular system (0.4%), respiratory system (0.3%).

The serious adverse event entries report 577 affected participants among 17084 at risk in the NuvaRing group and 751 affected participants among 17016 at risk in the combined oral contraceptives group. The other adverse event entries report 0 affected participants among 16864 at risk for NuvaRing and 0 among 16431 at risk for combined oral contraceptives. These are registry-reported counts, not the primary VTE comparison. The registry record does not report death values.

The listed serious-event categories include Digestive system at 1.0%, Genitourinary system at 0.8%, Injury, poisening, accidents, etc at 0.7%, Cardiovascular system at 0.4%, Respiratory system at 0.3%, and Psychiatric and neurological disorders at 0.3%. These entries are category percentages, not a detailed account of individual events. The registry record does not explain the category denominators or provide enough detail to determine whether a participant could contribute to more than one category.

General statistical context: adverse-event counts describe events recorded under the registry’s reporting definitions. They do not by themselves establish that an event was caused by a contraceptive, and they should not be substituted for the prespecified VTE endpoint. Because this comparison was not randomized, differences in recorded counts also require caution as causal evidence.

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

The registry record establishes that TASC aimed to characterize and compare risks associated with short- and long-term use of NuvaRing and marketed combined oral contraceptives. It identifies VTE as the primary endpoint and states that the analysis timeframe was within 48 months. It also records enrollment of 34100 and names the two user groups. These details describe the study question and structure, but they do not report the primary outcome result.

The posted record does not include VTE event counts, a group comparison estimate, a confidence interval, or a p-value. It therefore does not show whether the observed comparison favored either group, the size of any difference, or the precision of an estimate. The separate serious adverse event counts and categories do not fill this gap because they are not the primary endpoint results.

The record also does not establish a causal effect. The comparison was not randomized, and allocation is not stated. General statistical context: differences in outcomes between nonrandomized groups can reflect differences in exposure, participant characteristics, observation, or other factors. Without information about group comparability and the statistical adjustment used, the contribution of those factors cannot be assessed.

These limits are limits of the registry information, not proof that the study had no analyses or that no results exist elsewhere. The registry record does not report the details needed to appraise those analyses. Accordingly, the defensible reading is narrow: the record defines the intended VTE comparison and reports some safety counts, but does not provide the primary comparative result or enough analytical detail to support a conclusion about its magnitude or reliability.

14. Why This Trial Matters Statistically

This study raises a useful statistical question because it compares users of two contraceptive options in an active-surveillance setting and focuses on VTE, a time-to-event endpoint. The registry describes an objective spanning short- and long-term use, so the timing and duration of observation are relevant to understanding the question. Its endpoint definition also makes clear that the intended analysis concerns events among participants retained after protocol-violation exclusions.

The design makes interpretation especially dependent on the analysis details. The comparison was not randomized, and allocation is not stated. General statistical context: nonrandomized comparisons can be informative, but their interpretation depends on how participant differences, exposure, follow-up, and incomplete observation are handled. Those matters are not reported in the registry record. The listed enrollment cannot by itself show how many events informed the endpoint or how precise the comparison was.

The registry record lists 7 analyses as well as 2 outcome measures, but does not describe the analyses or any approach to multiplicity. This illustrates why outcome definitions and analysis plans matter: readers need to know which comparisons were intended and how uncertainty was assessed before weighing a reported estimate. In this record, the primary VTE result and its uncertainty are not reported, so those statistical questions remain unresolved.

The record is therefore informative about the intended comparison, endpoint, timeframe, and some safety reporting, while also illustrating the boundary between a registered study description and an interpretable outcome analysis. Its statistical importance lies in the question and design context; the available registry information does not support a quantitative conclusion about the primary endpoint.

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.

Several trial-specific details needed to interpret the VTE comparison are not reported in the registry record. These include the VTE event counts by group, the comparative estimate, its confidence interval, and the statistical test or model. Although the endpoint is described as a time-to-event analysis within 48 months, the record does not explain the time origin, censoring rules, or handling of incomplete follow-up.

The comparison was not randomized, and allocation is not stated. The record does not provide baseline characteristics or describe adjustment for differences between NuvaRing users and combined oral contraceptive users. It also does not report exposure histories, changes in contraceptive use, or how those changes were incorporated into analysis. These omissions prevent assessment of group comparability and potential confounding.

The endpoint population excludes participants removed for protocol violations, but the violations and number excluded are not reported. The registry record does not state how missing data were handled or identify other analysis populations. It lists 2 outcome measures and 7 analyses without specifying the analysis plan or multiplicity approach. The record also does not report the trial’s own sample-size justification or interim analyses.

Serious adverse event entries include participant counts and broad categories, but the record does not provide detailed event descriptions, explain category denominators, or report death values. These entries should not be mistaken for VTE results. Together, these limitations mean the registry information supports a description of the study question and reported safety fields, but not a full assessment of the primary comparative analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Transatlantic Active Surveillance on Cardiovascular Safety of NuvaRing (TASC) — NCT00524771.
• Registry record last updated 2014-04-09; status last verified 2014-03.
• Results first posted 2014-04-09.
• 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

TASC is a completed, nonrandomized active-surveillance comparison of NuvaRing users and users of combined oral contraceptives. The registry record lists enrollment of 34100, a study start of 2007-09, and primary completion in 2012-03. Its objective was to characterize and compare risks associated with short- and long-term use of the contraceptives.

The primary endpoint is the number of participants with VTE in a time-to-event analysis within 48 months. The registry record does not report the primary endpoint results, comparative estimate, or statistical precision. Serious adverse event counts and category percentages are reported separately, but they do not supply the missing VTE comparison. Allocation, analysis methods, missing-data handling, and the trial’s own sample-size justification are not reported in the registry record.