SPREAD-NET: PRactices Enabling Adapting and Disseminating in the Safety NET: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for SPREAD-NET: PRactices Enabling Adapting and Disseminating in the Safety NET (NCT02325531), a randomized na study. The primary outcome is Rate Ratio of the Percent of the Clinics' Patients "Indicated" for Statin With a Guideline-appropriate Prescription for Statins.

2. Clinical Question

3. Trial Design

SPREAD-NET was a pragmatic comparative-effectiveness trial with randomized allocation, no masking, and a parallel design. Clinics, not patients, were randomized to the support strategies. This is a cluster-randomized design: the unit assigned to an arm was the clinic, while the primary measure concerned clinic-level prescribing among patients meeting the monthly eligibility definition. Treating those patients as if each had been individually randomized would not reflect the trial design.

The four arms were low support, medium support, high support, and comparison. Low support included an EHR-based toolkit and basic webinar. Medium support included those elements plus staff training and adaptive webinars. High support added practice facilitation to the low- and medium-support components. The comparison arm received no researcher support; the description notes that the EHR-based toolkit was available to all clinics. The central contrast is thus among levels of support for clinic implementation, not among patient-level medication assignments.

The registry lists enrollment as 166, but the primary outcome description says the number of participants is unavailable and that only clinic-level data were collected. The enrollment figure should therefore not be interpreted as a count of patients contributing to the monthly endpoint or as a count of clinics. The record lists a start of 2014-09, primary completion of 2021-08, and status of completed. It lists Diabetes Mellitus and Cardiovascular Disease as conditions. The record does not report the number of clinics allocated to each arm or the details of the randomization procedure.

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: Data was collected at the clinic level, there was no data collected at the participant level and therefore there are no participant numbers available for any results modules.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The number of participants is not available for this study, only clinic-level data was collected.

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: This is a clinic randomized trial. No patients were recruited or consented in this study. Clinics were recruited and the intervention was conducted at the clinic level. Baseline data was collected on clinic rates. Only aggregate level data (percent of the population) was collected and it applied to clinics, not individuals.

6. Primary Endpoint

The registry lists the primary outcome as Rate Ratio of the Percent of the Clinics' Patients "Indicated" for Statin With a Guideline-appropriate Prescription for Statins, measured over Monthly, up to 48 months.

The primary endpoint is the rate ratio of the change in the percentage of a clinic’s indicated patients with a guideline-appropriate statin prescription. The denominator was defined monthly: it included patients with an in-clinic encounter during the previous year who were indicated for the medication under national guidelines that month. The registry describes measurement monthly, for up to 48 months. Because eligibility was reassessed over time, the group of patients contributing to the percentage could change from month to month and could be completely different across measurement times.

This endpoint focuses on implementation of prescribing practices at the clinic level. The trial’s stated purpose was to compare strategies for supporting clinic implementation of the ALL Initiative. The endpoint therefore tracks prescribing among patients indicated for statins, rather than measuring cardiovascular events or the effect of statin medication itself. A rate ratio expresses a relative comparison of changes; it does not, by itself, show the underlying percentages or how many patients contributed to them. General: implementation measures can help assess whether support strategies correspond to changes in care processes. The registry record does not report the numerical rate ratio or confidence limits, so the observed magnitude and precision cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a cluster-randomized, parallel trial and describes the primary measure as a rate ratio of change in a clinic-level percentage. It lists the summary measure as a mean and the dispersion measure as a 95% confidence interval. It does not report a statistical analysis plan, model specification, test results, or numerical estimates. The explanations below describe general statistical concepts and do not identify which particular model the investigators used.

Why clinic-level allocation matters

General: In cluster randomization, groups such as clinics are allocated to study arms, while measurements may be collected on people within those groups. Observations within one clinic can share local practices, staffing, and patient mix. This dependence means the effective information in the observations is not the same as if every patient had been independently assigned. Analyses commonly account for clustering, but the exact method must be reported before its assumptions can be assessed. The registry record does not state the model or its cluster-adjustment method. It does state that a simple individual-level re-analysis would be misleading, so no such recalculation is presented.

The randomized unit and outcome unit should also be kept distinct. Clinics were randomized, and the outcome is a percentage calculated for each clinic over time. The monthly denominator consists of patients meeting the encounter and guideline-indication criteria for that month. Patients may enter or leave that denominator as the months progress. A patient-level interpretation that assumes a stable group followed over the full period would not match the registry’s description.

What a rate ratio conveys

General: A rate ratio compares rates or relative changes on a ratio scale. Its meaning depends on exactly how the rates and changes were defined and modeled. The registry describes the value as the rate ratio of the change in the percentage of indicated clinic patients with a guideline-appropriate prescription. It does not give a formula, identify the reference contrast for each reported value, or state whether the estimate is adjusted. Those details are not reported in the registry record. The endpoint wording can therefore be explained, but the numerical contrast cannot be reconstructed.

A ratio is not the same as a percentage-point difference. It describes a relative relationship between quantities rather than the absolute difference between two percentages. General: absolute percentages and denominators help readers understand the practical scale behind a relative estimate. The record says the monthly percentages can be found in a publication referenced by the registry, but states that this is the only data available. It does not include those values in the outcome description used for this analysis. No absolute difference, ratio, or percentage can be calculated from the information in the registry record.

Confidence intervals and precision

General: A confidence interval expresses uncertainty around an estimate under a specified statistical procedure and its assumptions. A narrow interval indicates greater precision than a wide interval, while the estimate itself indicates the direction and scale of the result. A 95% confidence interval is named in the registry’s endpoint description, but neither the estimate nor the interval limits are reported. It is therefore impossible to judge whether the result was precise, compatible with a range of effects, or close to a reference value. The confidence level alone does not give the result.

The primary measure is also categorized as a mean of a continuous measure in the registry metadata, while its stated unit is a rate ratio. The endpoint description is the most informative explanation of what was measured: the rate ratio of the change in a clinic’s percentage. The record does not clarify this classification further. No additional interpretation of the statistical distribution or model should be inferred from the metadata alone.

Repeated monthly measurement and changing denominators

General: Repeated observations over time can be correlated, and their analysis may need to account for that pattern. In this trial, the registry describes monthly measurement for up to 48 months and explains that the denominator changed over time. It does not state how repeated measurements were modeled, whether all clinics contributed at every time point, or how incomplete monthly measurements were handled. Those analysis details are not reported in the registry record.

The changing denominator affects the question that a monthly percentage answers. It describes the share of currently eligible patients with an active, guideline-appropriate prescription according to that month’s criteria, rather than necessarily describing the same patients’ prescribing status across the entire measurement period. General: if the composition of a denominator changes, a trend in the percentage can combine changes in care with changes in the population being counted. The registry record does not include the month-specific counts needed to examine that composition.

Planning calculations are not observed trial results

General: Sample-size calculations based on an observed effect are planning illustrations, not evidence of the probability that the completed trial would find a result. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event calculations, the stated quantity is total events, while other calculations are expressed as participants per arm. These assumptions describe the illustrations, not the trial’s original design or its actual allocation.

The registry record does not report a sample-size justification, and the participant count for the primary outcome is unavailable. Any planning illustration should not be read as an observed sample size, a count of clinics, or observed power. General: observed power is not a substitute for interpreting an estimate and its uncertainty. Here, the numerical primary estimate and interval are not reported in the registry record, so no outcome-based planning value can be interpreted as a result.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and names two secondary outcomes: clinic characteristics associated with the effectiveness of the support strategies, and a rate ratio for change in the percentage of indicated patients with correct-intensity statin prescribing. The primary outcome is the rate ratio for change in the percentage with a guideline-appropriate prescription. The record does not specify the other outcome measures in the information available for this summary, nor does it report numerical results for the secondary outcomes.

Multiplicity arises when an analysis evaluates several outcomes, contrasts, time points, or subgroups. General: If many statistical tests are conducted, the chance of at least one apparently notable result can increase. Researchers may prespecify a primary comparison or use an adjustment strategy, but whether and how to do so depends on the protocol and analysis plan. A multiplicity strategy is not reported in the registry record. The record also does not state which contrasts among the support arms were considered primary, whether comparisons were prespecified, or how repeated monthly observations entered inferential testing.

Missing-data methods and analysis populations are also not reported in the registry record. The description establishes that the monthly denominator changed, but that is not the same as documenting missing observations or explaining how missingness was handled. The record does not say whether clinics with incomplete follow-up were included in every analysis, how missing monthly clinic measures were treated, or which analysis population was used. The number of participants is unavailable, and the reported primary data are clinic-level. These omissions limit assessment of the analysis, but do not establish that data were missing or that a particular method was used.

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

The registry record establishes what SPREAD-NET set out to compare: levels of clinic support for implementing the ALL Initiative, with statin prescribing among guideline-indicated patients as the primary outcome. It does not report numerical results for the primary endpoint. As a result, readers cannot determine from the record whether the prescribing measure increased or decreased, whether the arms differed, how large any contrast was, or how precisely it was estimated. A completed trial status does not supply those missing estimates.

The endpoint is a clinic-level implementation measure, not a measure of cardiovascular events. The trial description says the ALL Initiative was intended to reduce patients’ cardiovascular disease event risk, but the stated primary outcome concerns guideline-appropriate statin prescriptions. It would not be appropriate to treat the prescribing endpoint as a direct estimate of cardiovascular events or as proof of a patient-level health effect. The record does not report a primary outcome measuring such events.

The distinction between allocation and measurement is central. Clinics, rather than patients, were randomized. Monthly percentages were calculated from patients meeting the encounter and indication criteria for that month, and the record says those patients varied over time. The registry does not provide the number of clinics per arm, patient denominators by month, or numerical estimates and confidence limits. These gaps prevent assessment of the observed effect, precision, and the role of changing denominators.

General: a trial result supports conclusions only about the outcomes measured and the comparisons analyzed, subject to the design and analysis assumptions. Here, the registry description supports an account of the research question and design, but not a conclusion about which level of support performed better. It also does not justify a claim that the support strategies were equivalent, ineffective, or associated with a clinical benefit. The record’s reported zeros in adverse-event fields likewise should not be interpreted as proof that no adverse events occurred; their meaning is not clarified in the registry record.

12. Why This Trial Matters Statistically

SPREAD-NET is statistically notable because the randomized units were clinics while the outcome was constructed from patient prescribing within clinics. That distinction affects the analysis: observations from patients in the same clinic may share context, and statistical uncertainty needs to reflect the cluster-randomized design. A patient-level re-analysis that ignores this structure would not be a sound substitute for the trial’s own analysis. The registry record does not give enough model detail to assess how clustering was handled.

The endpoint also illustrates why denominators matter. Eligibility was reassessed monthly, using recent in-clinic encounters and the guideline indication for that month. The patients counted could change over time. A monthly percentage is therefore a summary of the eligible group at that time, not necessarily a repeated measure on a fixed cohort. Interpretation of change depends on both the prescribing measure and the composition of the changing denominator.

The trial separates implementation support from the clinical intervention being implemented. Its arms varied in the support delivered to clinics, while the primary outcome measured prescribing practice. This is a different statistical question from whether a medication changes clinical outcomes. Keeping that distinction clear prevents an implementation measure from being overinterpreted as a direct measure of patient health.

Finally, the record shows how design information can be more complete than result reporting. It provides the allocation structure, arm descriptions, outcome definition, schedule, and confidence-interval type, but no numerical primary result or analysis details. That gap means the design can be explained while the estimated effect and its precision remain unavailable. Statistical interpretation must reflect both what the endpoint was intended to capture and what the registry record does not report.

13. 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 the findings is that the registry record does not report the primary rate-ratio estimate, confidence-interval limits, or inferential test results. Without these values, the observed direction, magnitude, and precision cannot be assessed. The record also does not report numerical results for the listed secondary outcomes. The completed status does not resolve these reporting gaps.

The record states that only clinic-level data were collected for the primary outcome and that the number of participants is unavailable. Although enrollment is listed as 166, the record does not clarify in the primary outcome description what that figure represents. It should not be treated as the number of patients contributing to the monthly percentages or as the number of randomized clinics. The number of clinics in each arm is not reported.

The denominator varied monthly, and patient membership could change completely across measurement times. The record does not provide monthly denominator sizes, clinic-level prescribing percentages, or details about how incomplete measurements were treated. This limits assessment of changes in population composition and repeated-measure analysis. The statistical model, handling of clinic clustering, covariate adjustment, analysis populations, and multiplicity approach are not reported in the registry record.

The record identifies a 95% confidence interval as the dispersion measure without giving its limits, and it does not describe how the comparisons among arms were specified. The adverse-event entries list zero counts in the reported categories for each arm, but the record does not explain what those entries mean; they cannot establish that no adverse events occurred. These limitations apply to interpretation of the registry record and do not establish what may have been reported elsewhere.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: SPREAD-NET: PRactices Enabling Adapting and Disseminating in the Safety NET — NCT02325531.
• Registry record last updated 2022-12-13; status last verified 2022-11.
• Results first posted 2022-12-13.
• 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.

17. Record Summary

SPREAD-NET (NCT02325531) is a completed, randomized, parallel, unmasked pragmatic comparative-effectiveness trial sponsored by Kaiser Permanente. Clinics, not patients, were allocated to low, medium, or high support, or to a comparison condition. Support ranged from an EHR-based toolkit and basic webinar to additional staff training, adaptive webinars, and practice facilitation. The primary outcome was the rate ratio of change in the percentage of indicated patients with guideline-appropriate statin prescribing, measured monthly for up to 48 months.

The registry lists enrollment as 166, but says the number of participants is unavailable and that only clinic-level data were collected. It gives the endpoint definition and identifies a 95% confidence interval, but does not report the numerical primary result or its interval. Details of the statistical model, missing-data handling, and multiplicity approach are not reported in the registry record. The design and outcome question can therefore be described, but the size and precision of the observed effects cannot be evaluated from the registry record.