Toronto Thromboprophylaxis Patient Safety Initiative: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Toronto Thromboprophylaxis Patient Safety Initiative (NCT01869075), a randomized na study. The primary outcome is Percentage of Patients Prescribed Appropriate VTE Prophylaxis.

2. Clinical Question

The clinical question concerns implementation of recommended prevention practices rather than a direct comparison of medications. The endpoint counts patients who received prophylaxis meeting the study's criteria, relative to the patients at risk. Those criteria differ by clinical setting: they cover when prophylaxis was ordered and, depending on the setting, how long it was continued.

The registry describes rates for the active phases and says the comparison is between intervention and control. It does not report the actual rates, a difference between groups, or an uncertainty interval. The registry record therefore identifies the question and how the outcome was defined, but does not supply a numerical answer to whether the toolkit changed prescribing.

3. Trial Design

This was a randomized, parallel-group, single-masked trial of the Toronto Thromboprophylaxis Patient Safety Initiative, also called TOPPS. The registry labels the design as cluster randomized. The allocation unit and the identity of the masked parties are not reported in the registry record, so neither should be inferred from the design labels.

The intervention was a Knowledge Translation toolkit intended to support appropriate VTE prophylaxis. It included pre-printed orders, audit and feedback, pharmacist reminders to physicians, and staff education. The comparator was usual care. The six listed groups pair toolkit and usual-care arms within acute medical illness, major general surgery, and hip fracture surgery. The reported primary outcome population is 720 patients across those settings; the record states that phase 1 included 360 patients and phase 2 added 360 patients. Overall enrollment was 1895, which is distinct from the stated primary-outcome analysis population.

The study is marked completed. Its recorded start was 2006-07 and primary completion was 2009-03. The registry lists phase as NA. These design and timing details establish the broad structure, but do not reveal the number of clusters, how clusters were assigned, whether assignment was stratified, or how clustering was addressed in the analysis. Those details are not reported in the registry record.

The registry says that outcomes at the end of phase 2 are reported and gives a timeframe covering the duration of hospital stay. However, it does not provide the intervention and control outcome rates or a sponsor analysis estimate. Because allocation was clustered, a simple analysis that treats every patient as independently randomized would not respect the design; the record itself flags such an individual-level re-analysis as misleading.

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.

Before assignment: After site enrolment, baseline data was collected for all sites in order to establish sample size for phases 1 and 2.

Phase 0 (Baseline)

Phase 1

Phase 2

Analysis population for the primary outcome, as defined in the registry: The number of participants in the analysis was 720. In phase 1, there were 360 patients included and in phase 2, an additional 360 patients were included. The outcomes by end of study (end of phase 2) are reported. The patients in control (usual care) and intervention (Knowledge Translation toolkit) were compared.

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: Baseline data collection was conducted to establish baseline rates of appropriate prophylaxis. Baseline patients were not included in the active phases of the study.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Patients Prescribed Appropriate VTE Prophylaxis, measured over End of study (end of phase 2) - measured over duration of hospital stay..

The primary endpoint is the percentage of patients prescribed appropriate VTE prophylaxis. It is defined as the number of patients who received prophylaxis divided by the number of patients at risk. The registry says the outcome is assessed over the hospital stay and reported at the end of phase 2.

Appropriateness is setting-specific. For hip fracture surgery, the definition includes ordering evidence-based prophylaxis within 24 of admission, restarting it within 24 hours after surgery, and continuing it for at least 10 days post-discharge. For major general surgery, it includes ordering prophylaxis within 24 hours post-surgery and continuing it during the hospital stay. For acute medical illness, it includes ordering prophylaxis within 24 hours of admission and continuing it during the hospital stay. The record says the evidence-based choices were determined according to American College of Chest Physicians guidelines, with the 9th version current at the time of the study.

This process measure is relevant to the trial's quality-improvement question because it records whether recommended prophylaxis practices were followed. It is not itself a count of DVT or PE events, nor does the registry define it as a direct measure of those clinical outcomes. The endpoint description does not report the observed percentages or the comparison between arms.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information is limited. The registry identifies a cluster randomized, parallel-group design and a binary percentage endpoint, but does not report the statistical model, the sponsor's primary analysis, an effect estimate, a confidence interval, or a p-value. The general explanations below describe how such data are commonly interpreted; they do not establish which methods this trial used.

What does a percentage endpoint represent?

The endpoint is a proportion: the number of at-risk patients meeting the definition of appropriate VTE prophylaxis divided by the number of at-risk patients. General statistical context: a proportion describes how often a defined outcome was observed in a specified group. Comparing proportions between intervention and control can be expressed in several ways, including a difference in percentage points or a ratio. The registry does not report any such comparison, so none can be stated for this trial.

The underlying outcome is binary at the patient level: a patient either met the stated criterion or did not. The clinical criteria are not identical across settings, because the required ordering and duration differ. Combining such data requires a clear account of the populations and settings included and the analysis approach. That account is not reported in the registry record.

Why does cluster randomization matter?

General statistical context: cluster randomization assigns groups of people, such as clinical units or sites, rather than assigning each person independently. Patients in one cluster may share clinicians, workflows, or local practices. Their outcomes can consequently be correlated. If that correlation is ignored, the analysis may treat the data as containing more independent information than they actually do, leading to uncertainty estimates that are too narrow.

Appropriate methods for clustered data account for within-cluster similarity, for example through a model or variance calculation that reflects the assignment structure. The suitable method depends on design and data details. The registry does not report the number or identity of clusters, their sizes, the degree of within-cluster similarity, or the analysis method. It does explicitly state that a simple individual-level re-analysis would be misleading and that only the sponsor's own analysis is shown. However, the record lists no analyses and provides no numerical sponsor estimate. The analysis therefore cannot be independently interpreted from the reported record.

How should uncertainty be read?

General statistical context: a confidence interval describes a range of values compatible with the data and the assumptions of the analysis. It communicates precision as well as the estimated direction and magnitude of an effect. A narrow interval is more precise than a wide one, while an interval spanning values on both sides of no difference may leave the direction uncertain. A p-value, when reported, summarizes how unusual the data would be under a specified null model; it does not measure the probability that a treatment works or the size of an effect.

No confidence interval, p-value, or primary-effect estimate is reported in the registry record. There is therefore no basis to characterize statistical significance or precision. The absence of a reported estimate is not evidence that the intervention and control were equivalent; equivalence requires an appropriate design, analysis, and estimate with sufficient precision.

What can a planning illustration tell readers?

General statistical context: sample-size calculations use assumptions about the effect to detect, variability, allocation, and error rates. A planning illustration based on an observed effect is not a measure of the trial's achieved power, and it does not replace the study's original design justification. The record describes a planning illustration using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation, with the detectable effect set as a stated fraction of the observed effect. It says that the binary-outcome calculations are expressed as participants per arm; time-to-event calculations use total events. No numeric planning outputs or design justification are reported in the registry record. These assumptions should not be read as proof that the trial was designed or analyzed using the same approach.

In general, power is a property of a specified design and assumed effect, not a measure of whether a result is true. A post hoc calculation based on an observed effect does not recover the chance that the trial would have detected a clinically important difference. For this trial, the observed primary effect is not reported, so the registry information cannot support a numerical discussion of its magnitude or precision.

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("AMI - Knowledge Translation Toolkit", "AMI - Usual Care", "MGS - Knowledge Translation Toolkit", "MGS - Usual Care", "HFS - Knowledge Translation Toolkit", "HFS - Usual Care")
n      <- c(135, 105, 120, 120, 105, 135)
events <- c(86, 65, 80, 65, 89, 103)
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  AMI - Knowledge Translation Toolkit  135  86  63.7  55.0  71.8  55.3  71.3  55.3  71.3
ARM  AMI - Usual Care  105  65  61.9  51.9  71.2  52.4  70.6  52.3  70.6
ARM  MGS - Knowledge Translation Toolkit  120  80  66.7  57.5  75.0  57.8  74.5  57.8  74.5
ARM  MGS - Usual Care  120  65  54.2  44.8  63.3  45.3  62.8  45.2  62.8
ARM  HFS - Knowledge Translation Toolkit  105  89  84.8  76.4  91.0  76.7  90.4  76.6  90.4
ARM  HFS - Usual Care  135  103  76.3  68.2  83.2  68.5  82.7  68.4  82.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure: the percentage of patients prescribed appropriate VTE prophylaxis. It does not report analysis results. A count of one registered outcome measure does not establish that only one statistical comparison was planned or conducted; a prespecified testing hierarchy, multiplicity adjustment, and analysis plan are not reported in the registry record.

The primary endpoint is described across three settings and two care approaches. The record does not say whether the sponsor planned one combined comparison, separate setting-specific comparisons, or other subgroup analyses. It does not report how any multiple comparisons were handled. Without those details and the results, the risk of selective emphasis among possible comparisons cannot be assessed.

The endpoint description identifies 720 patients in the analysis population, with 360 included in phase 1 and an additional 360 in phase 2. It does not report missing outcome counts, reasons for missingness, exclusions from analysis, or whether the analysis followed an intention-to-treat principle. Nor does it describe imputation or sensitivity analyses. Those matters are not reported in the registry record and should not be inferred from the population count.

The record lists no analysis results, so there are no reported estimates with which to assess multiplicity or missing-data sensitivity. The cluster-randomized design also makes the analysis population and unit of analysis important, but the methods for handling clusters are not reported. These omissions limit assessment of both bias and precision.

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 1% reporting threshold.

The registry lists six groups: toolkit and usual-care groups within acute medical illness, major general surgery, and hip fracture surgery. In each group, the recorded serious adverse-event count is 0, and the recorded other adverse-event count is also 0. The corresponding group denominators are 135 and 135 for acute medical illness, 120 and 120 for major general surgery, and 105 and 135 for hip fracture surgery, in the order shown by the registry groups.

These figures describe the entries in the adverse-event record. They do not provide a comparison estimate or uncertainty interval, and they should not be read as proof that no adverse events occurred. The registry does not report adverse-event definitions, collection procedures, follow-up completeness, or a separate safety analysis. It also does not provide deaths counts. The listed safety counts do not answer the primary question about appropriate VTE prophylaxis prescribing.

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

The record shows that TOPPS was designed to compare a Knowledge Translation toolkit with usual care on a process outcome: the percentage of at-risk patients prescribed prophylaxis meeting setting-specific criteria. The intervention combined ordering tools, feedback, pharmacist reminders, and education. The study covered acute medical illness, major general surgery, and hip fracture surgery, and the primary outcome was described at the end of phase 2.

What the record does not show is the primary outcome result. There are no reported group percentages, effect estimate, confidence interval, or p-value. Accordingly, the direction and size of any difference, and how precisely it was estimated, cannot be assessed. The registry information does not establish that the toolkit improved prescribing, had no effect, or produced equivalent outcomes.

The outcome is a measure of whether appropriate prophylaxis was prescribed and continued according to the definitions given for each setting. It is not a direct report of DVT or PE events. Even if a prescribing difference were available, interpreting it as a change in clinical events would require outcome data and an analysis addressing that question; those results are not reported in the registry record.

The cluster-randomized design matters to interpretation because observations within clusters may be related. The record warns against a simple individual-level re-analysis but does not report the sponsor's numerical analysis. The recorded analysis population of 720 should also be distinguished from overall enrollment of 1895; the registry does not explain the difference. The listed zero adverse-event counts are descriptive entries, not proof of absence of risk or a substitute for complete safety reporting.

The most defensible reading is therefore descriptive: the registry specifies a quality-improvement intervention, a usual-care comparator, an implementation-focused endpoint, and the broad trial design. It does not provide the primary numerical findings needed to judge the observed comparison or its precision.

14. Why This Trial Matters Statistically

This trial is statistically notable because its intervention was evaluated through a cluster randomized design. When care practices are changed at a group level, the analysis must reflect that allocation structure. Treating patients as if each had been randomized independently can understate uncertainty when outcomes within clusters are correlated. The registry recognizes this issue and cautions that a simple individual-level re-analysis would be misleading.

The endpoint also illustrates a distinction between implementation and clinical outcomes. Appropriate prophylaxis prescribing is a process measure, defined by whether care met timing and duration criteria. The question is important to quality improvement, but it is not identical to whether patients experienced DVT or PE. A statistical interpretation must stay aligned with the outcome actually registered and reported.

The three clinical settings use different appropriateness criteria. That makes the endpoint clinically tailored, while also raising methodological questions about combining results across settings and whether effects vary by setting. The registry does not report setting-specific estimates or the analysis plan, so these questions remain unresolved in the record.

Finally, this case demonstrates why design descriptions alone are not enough to interpret effectiveness. The record gives enrollment, an analysis-population count, intervention details, and outcome definitions, but no primary outcome rates or effect estimate. Without those results and their uncertainty, the trial's central statistical comparison cannot be evaluated. Clear reporting of the cluster-aware analysis and its estimates would be needed to assess both magnitude and precision.

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 principal limitation for interpreting this trial from the registry record is that the primary outcome results are not reported. No intervention or control percentages, comparison estimate, confidence interval, or p-value is available. The record therefore permits no assessment of the direction, size, or precision of the primary result.

Although the design is identified as cluster randomized, the record does not give the number of clusters, their sizes, the assignment details, or the method used to account for clustering. Those omissions prevent evaluation of whether the analysis reflected the design and how much within-cluster correlation affected precision. The record itself warns that a simple individual-level re-analysis would be misleading.

The endpoint combines three settings with distinct criteria for appropriate prophylaxis, but setting-specific efficacy results and the planned approach to combining settings are not reported. The relationship between overall enrollment of 1895 and the primary analysis population of 720 is also not explained. Missing-outcome counts, reasons for exclusions, analysis-population definitions, and sensitivity analyses are not reported.

The registry does not report a statistical analysis plan, multiplicity procedures, or the sponsor's numerical analysis. Safety entries show zero serious and zero other events in each group, but event definitions and ascertainment details are not reported. These limitations concern what can be evaluated from the registry record; they do not establish that the study lacked those methods or data.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Toronto Thromboprophylaxis Patient Safety Initiative — NCT01869075.
• Registry record last updated 2014-09-23; status last verified 2014-09.
• Results first posted 2014-09-23.
• 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

The Toronto Thromboprophylaxis Patient Safety Initiative (TOPPS) is recorded as a completed, randomized, parallel-group, single-masked cluster trial sponsored by Sunnybrook Health Sciences Centre. Overall enrollment was 1895. The recorded start was 2006-07, and primary completion was 2009-03.

The trial compared a Knowledge Translation toolkit with usual care in acute medical illness, major general surgery, and hip fracture surgery. The primary endpoint was the percentage of at-risk patients prescribed appropriate VTE prophylaxis. Its description states that the analysis population was 720 patients, including 360 in phase 1 and an additional 360 in phase 2.

The registry does not report primary outcome estimates or a numerical sponsor analysis. It lists zero serious and zero other adverse events in each of the six groups. The cluster-aware analysis details, missing-data handling, and multiplicity procedures are not reported in the registry record.