Symptom Screening Linked to Care Pathways: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Symptom Screening Linked to Care Pathways (NCT04614662), a randomized na study. The primary outcome is Symptom Screening in Pediatrics Tool (SSPedi) Total Score.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group, cluster trial of symptom screening linked to care pathways for children with cancer. The registry record describes randomization of 20 pediatric cancer institutions, with intervention or control procedures applied at the site level. The reported enrollment was 445. Because assignment occurred by institution rather than separately for each participant, outcomes from participants at the same site may be related. That feature matters when estimating uncertainty and interpreting a comparison between groups.

The intervention combined three times weekly symptom screening through SPARK with feedback to healthcare providers and links to symptom-management care pathways. At control sites, participants received usual care. Usual care could include symptom screening or access to guidelines and pathways, but the registry does not state that these were consistently used. Participants in both groups completed SSPedi at weeks 0, 4 and 8 for outcome measurement; in the control group, these scores were not shared with providers or linked to care pathways.

The trial is listed as completed, with a start date of 2021-08-02 and primary completion date of 2023-10-18. Masking is recorded as none. The phase is recorded as NA. The registry lists fatigue, quality of life, symptom documentation, symptom-related interventions, and emergency department visits, unplanned clinic visits and hospitalizations among the secondary outcomes.

The posted record does not describe the sequence-generation procedure, how sites were allocated, whether allocation was concealed, or the number of sites in each group. It also does not report site-level characteristics or participant flow through follow-up. These details are relevant to assessing how well the groups were balanced and how completely outcomes were collected, but they cannot be inferred from the design label or enrollment figure.

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:

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 Symptom Screening in Pediatrics Tool (SSPedi) Total Score, measured over Week 8.

The primary endpoint was the Symptom Screening in Pediatrics Tool (SSPedi) total score at week 8. SSPedi measures how much 15 symptoms bothered a participant yesterday or today. Each symptom is scored on a 5-point Likert scale ranging from 0, not at all bothered, to 4, extremely bothered. The total score ranges from 0 to 60, with higher scores indicating more bothersome symptoms.

A total score combines responses across symptoms into a measure of overall symptom burden. It can provide a concise outcome for comparing groups, while necessarily compressing information about which symptoms contributed to a participant’s score. The registry describes SSPedi as reliable, valid and responsive to change in children with cancer 8-18 years of age.

The outcome is recorded as a mean with standard deviation, so a group summary would describe the average score and the spread of scores around that average. The registry record does not report the week 8 mean or standard deviation for either group, or a between-group estimate and confidence interval. It therefore does not show the observed magnitude or precision of the primary comparison.

The record also does not explain how a particular score difference should be judged in terms of importance to children or families. A statistical comparison and a judgment about clinical importance are related but distinct questions; the latter requires an interpretation standard that is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Why does the cluster design matter?

In an individually randomized trial, assignment is made separately for each participant. In a cluster-randomized trial, groups such as institutions are assigned, and participants within a group receive the same assigned approach. Here, the registry describes randomization of pediatric cancer institutions. Participants within one institution may share staff, clinical routines, and other features. Their outcomes can therefore be correlated even when they are different people.

General statistical principle: if the analysis treats correlated observations as independent, it can make the effective information in the data appear greater than it is and can produce confidence intervals that are too narrow. Analyses of cluster trials commonly account for the grouping in their uncertainty estimates. The registry notes that a simple individual-level re-analysis would be misleading, but the specific sponsor analysis method, any adjustment for clustering, and the assumptions used are not reported in the registry record. The number of institutions assigned to each group and any estimate of within-site correlation are also not reported.

What does a mean and standard deviation describe?

The primary measure is continuous and is summarized in the record as a mean with standard deviation. A mean describes the average score for a group. A standard deviation describes how spread out scores are around that average; it is not the uncertainty around the mean and is not a confidence interval for a treatment effect. Comparing group means can describe an average difference, but a complete statistical interpretation also needs an estimate of uncertainty that respects the cluster design.

General statistical principle: a confidence interval for a between-group effect communicates both the estimated difference and its precision under the stated model. The interval depends on the data and the analysis assumptions. The registry record does not report group means, standard deviations, an effect estimate, or a confidence interval for the primary endpoint, so those quantities cannot be interpreted for this trial.

What is the role of the primary endpoint?

A primary endpoint identifies the principal outcome used to address the main trial question. In this trial, the primary endpoint is the SSPedi total score at week 8. The tool asks about 15 symptoms and uses a score from 0 to 60, where higher values indicate more bothersome symptoms. Choosing a specified outcome and time point can focus interpretation, but the registry record does not report the statistical analysis plan or explain how the week 8 comparison was modeled.

The endpoint is a participant-reported measure. Such measures capture the participant’s experience directly, while relying on participants to complete the questionnaire as intended. The registry describes SSPedi’s measurement properties for children with cancer 8-18 years of age. It does not report how questionnaire completion was supported, how incomplete responses were scored, or how outcome data were checked.

How should the planning illustrations be read?

The sample-size illustrations are planning calculations based on the observed effect, not the trial’s own design. They use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the target effect is expressed as a stated fraction of the observed effect. The registry describes the non-time-to-event illustrations as participants per arm for 80% or 90% power. Such values are hypothetical planning quantities: they describe the sample size a future study might require under those assumptions and effect targets. They are not the number of people observed in this trial, and they are not observed power.

General statistical principle: planning calculations depend on assumptions about the target effect, variability, allocation, and analysis. For a cluster-randomized design, clustering also affects the information available and generally needs to be incorporated into a design calculation. The listed assumptions do not describe the original trial’s sample-size justification, and that justification is not reported in the registry record. No numerical planning estimates or observed primary effect are reported in the registry record, so no planning value can be interpreted against an observed result.

What cannot be determined from the listed methods?

The registry record does not report whether the primary comparison used an unadjusted or adjusted model, what variables were included, how site clustering was handled in the sponsor analysis, or whether any sensitivity analyses were conducted. The statistical plan, model diagnostics, and interim analyses are not reported in the registry record. These are not details that can be inferred from the fact that the trial was randomized or from the measurement scale.

General statistical principle: an analysis should match the way treatment was assigned and should make its assumptions transparent. Adjustment can sometimes improve precision or address chance imbalance, but the choice of variables and model must be justified and specified. Without the sponsor’s analysis description and numerical results, readers cannot evaluate those choices for this trial. The registry record’s design information supports the caution against a simple individual-level re-analysis, but does not support reconstructing the sponsor’s analysis or its result.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Intervention", "Control")
n   <- c(198, 213)
m   <- c(7.9, 11.4)
sp  <- c(7.2, 8.7)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Intervention  198  7.900  7.200  6.891  8.909
CARM  Control  213  11.400  8.700  10.225  12.575

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and several secondary outcomes, including fatigue, quality of life, symptom documentation, provision of symptom interventions, and emergency department visits, unplanned clinic visits and hospitalizations. It records 6 outcome measures. Examining multiple outcomes can raise a multiplicity issue: when many statistical comparisons are made, the chance of at least one apparently notable finding can increase. General statistical approaches include defining a hierarchy of outcomes or adjusting inference across a family of comparisons. Which, if any, approach was used is not reported in the registry record. The record also does not report the secondary outcome results or their analysis plan.

Missing outcome data can affect interpretation if participants with observed outcomes differ systematically from those without them. General approaches include describing the amount and pattern of missingness, stating assumptions about why data are missing, and conducting appropriate sensitivity analyses. The registry record does not report completion rates for SSPedi, missing-data handling, reasons for missing assessments, or sensitivity analyses. The reported enrollment does not establish how many participants contributed to the week 8 analysis.

The analysis populations are not reported in the registry record. It does not state whether the sponsor analyzed participants according to their site’s randomized assignment, whether any other population was used, or how site and participant withdrawals were handled. It also does not describe deviations from assigned procedures. These omissions limit assessment of whether the reported analysis, if available, would preserve the cluster-randomized comparison and how representative the analyzed participants were of those enrolled.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The adverse-event figures list 0 serious adverse events among 221 participants at risk in the intervention group and 0 among 224 participants at risk in the control group. Other adverse events are also recorded as 0 in each group, and deaths are recorded as 0 in each group. No top serious adverse-event terms are listed.

These figures describe what is recorded in the registry for the stated at-risk groups. They should not be expanded into a claim that no symptoms, complications, or safety concerns occurred during the trial. The registry record does not provide further detail on adverse-event definitions, collection procedures, observation periods, severity categories beyond the serious and other categories, or the completeness of safety reporting. It also does not explain how safety events were attributed or analyzed.

Zero recorded events in these categories do not establish that an intervention is free of risk. The figures are best read narrowly: the registry reports zero affected participants for the listed categories in each group. They do not replace the primary symptom-burden outcome or provide information about its treatment effect, which is not reported in the registry record.

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

This trial addressed a practical clinical research question: whether frequent symptom screening, provider feedback, and links to symptom-management pathways could change reported symptom burden for children with cancer compared with usual care. The registry identifies the cluster-randomized design, the intervention components, the comparator, and SSPedi total score at week 8 as the primary endpoint. It also describes secondary measures related to fatigue, quality of life, symptom documentation, symptom interventions, and healthcare use.

The registry record does not report the primary endpoint result, an effect estimate, a confidence interval, or a primary p-value. It therefore does not establish the direction, size, or precision of a difference between the trial groups. The completed status and enrollment figure do not fill that gap. Nor do the zero adverse-event counts answer the primary question about symptom burden.

If a group difference were reported, its meaning would depend on the estimated size, its uncertainty, and the validity of the analysis. Statistical evidence and clinical importance are distinct: a result can be estimated precisely yet be small, or estimated imprecisely enough to leave a wide range of plausible effects. The registry record does not provide an interpretation threshold for SSPedi score differences, so it cannot establish what size of difference participants or clinicians would consider important.

The cluster design also means that the analysis needs to account for site-level assignment and possible similarity among participants within sites. The record cautions that simple individual-level re-analysis would be misleading, while the sponsor’s numerical analysis is not reported. Detailed interpretation would require that analysis and information about follow-up, missing data, outcome definitions, and any multiplicity procedures.

Accordingly, the registry record supports understanding what was tested and how the primary outcome was defined. It does not support a conclusion that the intervention did or did not change symptom burden, nor does it establish the magnitude or reliability of any treatment effect. Those questions remain unanswered by the results reported in the registry record.

14. Why This Trial Matters Statistically

The trial is statistically notable because treatment was assigned at the institution level while the primary outcome was measured in individual children. That mismatch between the unit of assignment and the unit of measurement is common in cluster trials and has important consequences: participants within the same institution may share circumstances that make their outcomes more alike. A sound analysis must reflect the randomized clusters when estimating uncertainty.

The comparison also has a pragmatic feature. Usual care could include symptom screening, guidelines, or care pathways, while intervention sites were prompted to use a specific screening and feedback system linked to pathways. This variation means the contrast is between the assigned intervention approach and usual care as practiced, rather than a guaranteed absence of all symptom-related care in the control group. The registry does not report how these practices varied across sites.

SSPedi provides a participant-reported measure of how bothersome a range of symptoms were over a recent period. Its total score makes an overall symptom-burden comparison possible, while the listed secondary outcomes broaden the questions to fatigue, quality of life, documentation, interventions, and healthcare use. The record describes the outcome set but does not report comparative results.

The most important statistical limitation for interpretation is the absence of the numerical primary analysis and its methods in the registry record. This prevents readers from evaluating the size and precision of the main effect or checking how clustering was handled. It also illustrates why a trial’s design and outcome definitions, though essential, cannot substitute for transparent reporting of estimates, uncertainty, missing data, and analysis choices.

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 registry record leaves several trial-specific details unavailable for assessing the results. It does not report the numerical primary endpoint comparison or the sponsor’s statistical method, despite noting that a simple individual-level re-analysis would be misleading because of the cluster-randomized design. Without the analysis and its cluster adjustment, the uncertainty around the primary comparison cannot be evaluated.

The record describes randomization of 20 institutions but does not report how many institutions were assigned to each group, how assignment was conducted, or whether allocation was concealed. It also does not provide site-level characteristics, participant flow, or the number with week 8 SSPedi data. These gaps prevent assessment of site balance, attrition, and the extent to which the analyzed participants represent those enrolled.

Usual care could include symptom screening, guidelines, or care pathways, but the record does not describe how often these elements were used at control sites. It also does not report adherence to intervention screening, provider feedback, or pathway use across intervention sites. Without such information, the extent of separation between assigned care approaches cannot be assessed.

The registry does not report missing-data procedures, analysis populations, multiplicity handling, or outcome-specific statistical methods. It also does not give a clinical interpretation threshold for the SSPedi total score. These limitations apply to interpretation of the registry record; they do not establish that the trial investigators failed to collect or analyze these details.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Symptom Screening Linked to Care Pathways — NCT04614662.
• Registry record last updated 2025-09-23; status last verified 2025-09.
• Results first posted 2025-09-23.
• 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 registry record describes a completed, randomized, parallel, cluster trial of symptom screening linked to care pathways for children with cancer. It lists an enrollment of 445 and describes randomization of 20 pediatric cancer institutions. Intervention sites used SPARK for prompted symptom screening three times weekly, with feedback and links to symptom-management pathways for healthcare providers. Control sites provided usual care, which could include symptom screening or access to guidelines and pathways.

The primary outcome was SSPedi total score at week 8, recorded as a mean with standard deviation. The registry explains that higher scores indicate more bothersome symptoms. It does not report the primary outcome results or the sponsor’s numerical analysis. The record also does not report statistical methods for the primary comparison, missing-data handling, or multiplicity procedures. It records zero serious and other adverse events, and zero deaths, in each listed group.