Family History and Cancer Risk Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Family History and Cancer Risk Study (NCT05079334), a registered phase not stated study. The primary outcome is MeTree Completion (REACH).

2. Clinical Question

The study asks whether deploying MeTree can support collection and use of family health history, including identification of participants at high risk of hereditary cancer. The primary endpoint concerns engagement with the platform: among participants sent a MeTree link, how many complete the questionnaire sufficiently to generate a risk report? The study description also frames the work as an assessment of the efficiency of MeTree compared with completing pedigrees in clinic. The registry record does not describe a randomized comparison or state how any comparison groups were formed.

3. Trial Design

This is a family health history study involving investigators from Vanderbilt University Medical Center, Duke University, and Meharry Medical College. Vanderbilt University Medical Center is listed as the sponsor. The registry record gives an enrollment of 1847 and describes participants completing surveys and the MeTree questionnaire. MeTree uses questionnaire responses to determine cancer risk based on current guidelines. The study team is described as offering genetic counseling to participants identified as high risk and tracking participant outcomes and behaviors.

The stated aim includes assessing the efficiency of MeTree compared with completion of pedigrees in clinic. However, the registry record identifies the study as not a randomized comparison, does not state allocation, and does not provide enough detail to characterize how participants entered any comparison groups. The groups therefore cannot be assumed to be exchangeable or to provide a like-for-like control comparison. Further details of the comparison procedure are not reported in the registry record.

The study start date is 2022-01-01, the primary completion date is 2025-08-31, and the status is COMPLETED. The primary endpoint timeframe is from enrollment to study completion, up to 3 years. The registry record lists secondary outcomes concerning EHR-based identification for high risk of hereditary cancer and genetic counseling appointment lengths. It also records 3 outcome measures and 3 analyses, but does not provide the detailed analysis populations or a complete account of the methods used for each outcome.

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

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 participants who were eligible and consented in the study

6. Primary Endpoint

The registry lists the primary outcome as MeTree Completion (REACH), measured over From enrollment to study completion (up to 3 years).

The primary endpoint, MeTree Completion (REACH), measures completion of the family health history questionnaire among participants sent a MeTree link. Completion is defined operationally as generation of a MeTree risk report. This definition makes the endpoint a count or proportion of participants reaching a specified platform output, rather than a measure of cancer diagnosis, hereditary-risk accuracy, or subsequent health outcomes.

Engagement steps such as clicking the link and creating an account are to be summarized descriptively. These steps can distinguish different stages of engagement, but the registry record does not give their results. It also specifies 95% confidence intervals for the completion proportion using the Wilson method, with exploratory subgroup comparisons by site and demographics.

Completion is relevant to evaluating whether participants engage with a digital family-history process. It does not by itself establish whether the information is complete or accurate, whether risk classification is correct, or whether care changes. The number of participants sent a link, the number generating risk reports, the resulting proportion, and its confidence interval are not reported in the registry record. The enrollment count is not identified as the primary endpoint denominator.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary completion event: a participant either generates a MeTree risk report or does not. For this kind of outcome, a count describes how many participants experienced the event, while a proportion relates that count to a defined denominator. Here, the intended denominator is participants sent a MeTree link. The registry record does not report the count or denominator needed to state the observed proportion.

The record specifies 95% confidence intervals using the Wilson method. In general, a confidence interval expresses the uncertainty around an estimate in a way that reflects the information available in the data. For a proportion, the Wilson method is one approach to forming an interval. It is often useful because interval behavior for proportions can be less satisfactory with simpler methods, particularly when event counts or proportions are near the boundaries. This is a general explanation of the method; the registry record does not give the interval endpoints or the data used to calculate them.

The endpoint's operational definition matters for interpretation. A risk report is the recorded completion criterion, so the endpoint captures reaching that platform output. It does not establish that every questionnaire item was answered in a particular way, that the entered family history was verified, or that the risk report was clinically accurate. Those properties are not defined as part of the primary endpoint in the registry record.

The registry description says link clicks and account creation will be summarized descriptively. In general, descriptive summaries characterize observed data without necessarily estimating a causal effect. These engagement steps can help distinguish initial interest from later completion, but they are not the primary completion definition. No results for these steps are reported in the registry record.

Subgroup comparisons by site and demographics are designated exploratory. In general, exploratory comparisons can identify patterns for further study, but they are not equivalent to a prespecified confirmatory test unless the analysis plan supports that interpretation. Their precision depends on how many participants contribute to each group and on the outcome distribution within those groups. The registry record does not report subgroup counts, estimates, confidence intervals, or a detailed plan for handling multiple subgroup comparisons.

The study's stated comparison concerns MeTree and completion of pedigrees in clinic, but this is not a randomized comparison and allocation is not stated. In general, random assignment can help make comparison groups similar with respect to factors that affect outcomes. When allocation is not randomized, observed differences can also reflect differences in who entered each group, how each process was implemented, or other factors. The registry record does not give enough information to determine how such issues were addressed, and it does not describe the groups as like-for-like controls.

The registry record includes planning-illustration assumptions: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are described as planning assumptions, not as the trial's own design justification. The calculated illustration values and the observed effect are not reported in the registry record. Such planning illustrations are not observed power and do not show the probability that the completed study detected an effect.

In general, over-dispersion matters when observed outcome variability exceeds what an assumed statistical model allows; ignoring it can make uncertainty estimates too small. The primary endpoint is a binary outcome, and the registry record specifies a Wilson interval for its proportion. It does not report an over-dispersion analysis for this endpoint, so no such adjustment should be inferred. Other outcomes may use different statistical approaches, but their analysis methods are not reported in the registry record.

The record does not report whether estimates were adjusted for covariates, how missing endpoint data were handled, or whether analyses followed an intention-to-treat or other population definition. Those omissions prevent a fuller assessment of the analysis choices and the population represented by any estimates.

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("Reach")
n      <- c(1847)
events <- c(1847)
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  Reach  1847  1847  100.0  99.8  100.0  99.8  100.0  99.8  100.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 3 outcome measures and 3 analyses. It identifies MeTree Completion (REACH) as the primary outcome and names secondary outcomes concerning EHR-based identification for high risk of hereditary cancer and genetic counseling appointment lengths. It also states that subgroup comparisons by site and demographics are exploratory. The record does not report a multiplicity adjustment or explain whether one was planned. Without that information, the degree to which the analyses account for the possibility of chance findings across multiple outcomes or subgroups is unclear.

Missing-data methods are not reported in the registry record. In general, missing outcome information can affect an estimate if participants without recorded results differ from those with observed results. For the primary endpoint, interpretation requires knowing how many participants were sent a link and how participants without a generated report were classified or handled. The record does not give these details, the number of missing observations, or a sensitivity analysis.

The analysis populations are also not described. The enrollment count is 1847, but the registry record does not state whether all enrolled participants contributed to each analysis, or how eligibility, link distribution, withdrawal, or incomplete questionnaires affected the analysis sets. It would therefore be inappropriate to assume that enrollment is the denominator for the completion outcome.

The record describes a nonrandomized comparison and does not state allocation. It does not report how participants were selected into comparison groups or whether differences between groups were addressed in analysis. These limitations are distinct from multiplicity and missing-data concerns, but they also affect how comparisons should be interpreted.

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

The registry record describes a study intended to evaluate the use of MeTree for collecting family health history and supporting identification of hereditary cancer risk. The primary endpoint is defined in terms of questionnaire completion, with generation of a risk report serving as the completion criterion. This is a measure of platform engagement, not a direct measure of diagnostic accuracy or improved health outcomes.

The central numerical result needed to interpret that endpoint is absent: the registry record does not report the number of participants sent a link, the number who generated a report, the completion proportion, or the confidence interval. The enrollment of 1847 does not substitute for the stated denominator. As a result, the registry information does not establish how common completion was or how precisely it was estimated.

The study description includes a comparison with clinic pedigree completion, but the comparison is not randomized, allocation is not stated, and the groups are not described as like-for-like controls. Any comparative interpretation would require details about group formation, outcomes, denominators, and analysis that are not reported in the registry record.

The registry record's description of offering genetic counseling to high-risk participants explains an intended part of the study process. It does not report whether participants attended counseling or whether risk identification changed care. Likewise, the named secondary outcomes do not establish findings because their results are not reported.

The adverse-event entries list zero events alongside zero participants at risk. Those entries cannot be read as evidence of zero events among the enrolled study population without further information about the reported denominator. Overall, the record supplies study context and an endpoint definition, but not the primary outcome estimate needed to assess observed completion.

13. Why This Trial Matters Statistically

Family health history collection can involve steps between inviting a participant and generating information that can be used for risk assessment. The endpoint definition makes one of those steps measurable: completion is recorded when a MeTree risk report is generated. Distinguishing completion from link clicks or account creation is statistically useful because those are different stages of engagement rather than interchangeable outcomes.

The endpoint also illustrates why denominators matter. A completion proportion among participants sent a link answers a different question from a count among all enrolled participants. The registry record reports enrollment but not the link-sent denominator or the number generating risk reports. Without both, neither the observed completion level nor its precision can be assessed.

The registry record specifies a Wilson confidence interval for the primary proportion and identifies subgroup comparisons as exploratory. These choices make the intended statistical framing visible: estimation of a proportion, with uncertainty, and cautious investigation of variation across sites and demographic groups. The actual estimates and intervals are not reported, so the intended methods cannot be evaluated against results.

The nonrandomized comparison is also statistically important. Comparing a web platform with clinic pedigree completion may be informative, but differences between groups cannot be interpreted as effects of the platform without understanding how participants entered each group and how relevant differences were handled. The registry record does not give those details.

Finally, separating platform completion from risk classification, counseling, and subsequent outcomes helps keep claims aligned with what the endpoint measures. A completion measure can describe engagement with a process; it does not alone establish the accuracy or downstream consequences of that process.

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 main limitation for interpreting the primary endpoint is that its result is not reported in the registry record. The number sent a MeTree link, the number generating a risk report, the estimated completion proportion, and the 95% confidence interval are all absent. The enrollment count of 1847 does not resolve this gap because the endpoint denominator is defined as participants sent a link, and the record does not say that those counts are the same.

The comparison with clinic pedigree completion is difficult to assess. The registry record states that the study is not randomized and does not state allocation. It does not describe the comparison groups, their sizes, their baseline characteristics, or how differences between them were analyzed. The record itself cautions that the arms are not a like-for-like control comparison.

The primary endpoint records generation of a risk report, but the registry record does not report validation of the information entered or the accuracy of risk classification. It also does not report results for the named secondary outcomes, including EHR-based identification of high risk or genetic counseling appointment lengths. The study description mentions an offer of genetic counseling to high-risk participants, but counseling uptake and later outcomes are not reported.

Methods for missing data, analysis populations, covariate adjustment, and multiplicity are not reported in the registry record. Subgroup analyses are described as exploratory, but the subgroup results and their precision are absent. Finally, the adverse-event listing gives zero participants at risk, leaving the context for its zero event counts unclear.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Family History and Cancer Risk Study — NCT05079334.
• Registry record last updated 2026-06-24; status last verified 2026-06.
• Results first posted 2026-02-10.
• 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.

18. Record Summary

NCT05079334, titled Family History and Cancer Risk Study, is listed as COMPLETED. Vanderbilt University Medical Center is the sponsor, with investigators from Vanderbilt University Medical Center, Duke University, and Meharry Medical College described as collaborators. The registry record lists enrollment of 1847, a study start date of 2022-01-01, and a primary completion date of 2025-08-31.

The study describes deploying MeTree, a web-based family health history platform, and tracking outcomes and behaviors in relation to completion of pedigrees in clinic. The primary endpoint is MeTree questionnaire completion, defined by generation of a risk report, with a stated timeframe from enrollment to study completion, up to 3 years. A Wilson method 95% confidence interval is specified, and site and demographic subgroup comparisons are exploratory.

The registry record does not report the primary completion estimate, its denominator, or its confidence interval. It identifies the comparison as nonrandomized, with allocation not stated, and lists secondary outcomes concerning EHR-based identification of hereditary cancer risk and genetic counseling appointment lengths.