Evaluation of the Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together Program: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of the Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together Program (NCT04335279), a randomized na study. The primary outcome is Anxiety: Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety 4a v1.0.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, parallel-group trial with no masking. It identifies the design as partially nested: participants in intervention training groups may be dependent on one another, while the wait-list participants are not described as receiving group training. This feature matters because outcomes among people sharing intervention sessions may be more alike than outcomes from unrelated participants. The registry record does not report the planned statistical handling of that dependence.

The trial is described as pragmatic and conducted using an existing systemic sclerosis patient cohort. The registry enrollment is 172. The record lists a start date of 2020-04-09, a primary completion date of 2020-06-03, and a completed status. The posted primary outcome counts are 78 in the SPIN-CHAT group and 83 in the wait-list group. These are outcome counts, not a substitute for the enrollment figure, and the registry record does not explain the difference.

The intervention was a brief group videoconference program aimed at worry and anxiety, scheduled 3 times per week for 4 weeks. Each group was to include 8 participants. The duration description for each session is truncated in the registry record, so a complete session length is not reported there. The wait-list group did not receive the program during the trial and was to receive access post-trial.

The primary outcome was anxiety at 4-weeks post-randomization. Anxiety was also recorded as a secondary outcome at 10-weeks post-randomization. The record lists other secondary measures addressing depression symptoms, loneliness, boredom, physical activity, adverse effects, and fear related to COVID-19. It does not report the original sample-size justification, detailed allocation procedures, or the planned analysis model.

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: There were 560 eligible participants based on baseline questionnaires, of whom 246 indicated they were interested in participating in the trial; of these, 58 could not be reached to confirm enrolment and 16 were not randomly assigned owing to inability to match language or day and time availability. Thus, 172 were eligible and randomly assigned to intervention (n=86) or waitlist control (n=86). Of the 172, 93 (54%) were ongoing SPIN Cohort participants, and 79 (46%) were new participants.

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.

6. Primary Endpoint

The registry lists the primary outcome as Anxiety: Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety 4a v1.0, measured over 4-weeks post-randomization.

The primary endpoint is the mean PROMIS Anxiety 4a v1.0 T-score at 4-weeks post-randomization. The measure has 4 items asking how often participants experienced fear, difficulty focusing beyond anxiety, overwhelming worries, and uneasiness during the past 7 days. Each item uses a 5-point response scale from “never” to “always.” Raw responses are converted to T-scores standardized in the US adult general population, where the reference mean is 50 and the standard deviation is 10. Higher scores represent more anxiety.

A continuous score retains gradations in reported symptoms rather than reducing each participant to a yes-or-no category. Comparing group means therefore describes the average score difference at the assessment time. The PROMIS measure offers a standardized way to express responses and is intended to capture anxiety symptoms that the intervention sought to address. Standardization does not mean that every individual score is precise, nor does a group mean describe every participant’s experience.

The registry record also names anxiety at 10-weeks post-randomization as a secondary assessment. That later measurement concerns the same symptom domain at a different time; it is not the primary endpoint. Interpretation of either time point depends on the observed score distributions, the analysis approach, and how missing outcome data were handled. The registry record does not report details of those analysis procedures.

7. Results Posted in the Registry

• SPIN-CHAT: Videoconference Intervention: mean 56.90 versus 58.80 on control; difference -1.90 (95% CI -4.06 to 0.26), standardized effect d = -0.27; z-test p = 0.085.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Anxiety: Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety 4a v1.0

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • SPIN-CHAT: Videoconference Intervention: mean 55.10 versus 58.20 on control; difference -3.10 (95% CI -5.49 to -0.71), standardized effect d = -0.41; z-test p = 0.011.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for SPIN-CHAT: Videoconference Intervention than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry record lists secondary measures for anxiety, depression symptoms, loneliness, boredom, physical activity, adverse effects, and fear related to COVID-19. It also contains numerical results for anxiety at 10-weeks post-randomization. The record does not provide numerical comparisons for the other named secondary measures in the posted results, so no direction or size of difference for those outcomes can be inferred from their inclusion in the registry.

The later anxiety result concerns the same general symptom construct as the primary outcome but at a different assessment time. Its unadjusted comparison is more separated from zero than the primary comparison. This offers additional context about anxiety after the primary measurement, but it does not resolve the primary result or demonstrate a change in the group difference over time. A direct test of a time-by-group pattern is not reported in the registry record.

Secondary findings generally carry less confirmatory weight than the primary endpoint because they are additional opportunities to observe a result that may appear notable by chance. The record lists multiple secondary outcomes, but it does not report a multiplicity strategy, outcome hierarchy, or a prespecified interpretation plan. Without that information, an isolated unadjusted secondary result should be treated as suggestive evidence that may need confirmation, rather than as an independent definitive conclusion.

Secondary measures can still help characterize the range of questions addressed in a trial and can motivate further research. Their value depends on transparent reporting of how they were selected, analyzed, and interpreted. The registry record does not report detailed results for all the listed secondary measures or how missing data were handled for them. The overall secondary evidence therefore remains limited in what it can say about effects beyond the posted later anxiety comparison.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Anxiety: Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety 4a v1.0
• Depression Symptoms: Patient Health Questionnaire (PHQ-8)
• Loneliness: University of California, Los Angeles (UCLA) Loneliness Scale (ULS-6)
• Boredom: Multidimensional State Boredom Scale (MSBS-8)
• Physical Activity: International Physical Activity Questionnaire - Modified for the Elderly (IPAQ-E)
• Adverse Effects
• Fear: COVID-19 Fears Questionnaire for Chronic Medical Conditions

9. Statistical Interpretation

10. Statistical Methods Explained

For a continuous endpoint, the group mean is the arithmetic average of observed scores, and the standard deviation describes how spread out individual scores are around that average. The primary outcome is reported as a mean and standard deviation for each group. This gives a compact account of the score level and variability, but it does not show the full distribution, identify outliers, or explain how participants with missing scores were treated.

What does the mean difference represent?

The mean difference compares the intervention-group mean with the control-group mean. In the posted comparisons, the direction is SPIN-CHAT minus wait-list control. A negative mean difference therefore means the intervention-group mean score is lower than the control-group mean score. Because higher PROMIS anxiety scores represent more anxiety, a negative difference describes a lower average anxiety score in the intervention group at that assessment. This is a description of the measured group means, not a causal conclusion on its own.

For the primary assessment, the posted group means are 56.9 and 58.8, and the mean difference is -1.9. The associated unadjusted interval includes zero. The unadjusted p-value is 0.085. A p-value is a measure of how inconsistent the observed data are with a specified null model, assuming that model and its assumptions apply. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of a difference.

Why does the design matter?

The trial is described as partially nested because intervention participants took part in groups. As a general statistical point, people in the same group can share experiences or influences, making their outcomes correlated. If such dependence is ignored, standard errors and confidence intervals may be inaccurate. A partially nested analysis can account for clustering on the intervention side without assuming equivalent training groups in the control arm. The registry record does not report whether or how the analysis accounted for this feature, so the posted unadjusted calculations should not be treated as confirmation that clustering was handled.

Random allocation is intended to make comparison groups similar on average with respect to measured and unmeasured factors, but it does not guarantee balance in a particular trial. Masking is listed as none. The registry record does not specify whether outcome collection or analysis involved any other masking arrangement. The number of participants contributing to an outcome can also differ from overall enrollment, so interpretation should distinguish the enrolled population from the outcome-specific counts.

What does an unadjusted calculation leave out?

The posted comparison is a simple unadjusted re-calculation from group summary statistics. It does not incorporate covariate adjustment, repeated measurements, clustering, or other model features unless these are represented in the summary statistics; the registry record does not describe such a model. The displayed p-values and confidence intervals should therefore be understood as unadjusted summaries rather than a complete reconstruction of a prespecified trial analysis. The registry record does not report a sponsor analysis result or detailed statistical analysis plan for the primary comparison.

For continuous outcomes, the standard error reflects uncertainty in estimating a group mean or a difference between means. It depends on sample size and variability. As a general statistical point, a larger standard error tends to produce a wider confidence interval, all else being equal. The posted arm counts and standard deviations are part of the information used in simple comparisons, but a more complex design can alter the appropriate uncertainty calculation.

Effect size is another way to describe a difference relative to variability. The posted primary standardized difference is -0.273. A standardized measure can help compare outcomes expressed on different scales, but it does not give a direct clinical interpretation. Its meaning depends on the variability in the population and on whether the scale captures a meaningful difference to participants. The registry record does not identify a clinically important difference threshold for this anxiety measure.

The registry record describes several secondary outcomes and a later anxiety assessment. When multiple outcomes or time points are examined, a notable result can arise by chance even if there is no true difference for any of them. As a general statistical point, multiplicity procedures can control the overall chance of false-positive findings, but they can also affect the precision or power of individual comparisons. Whether a correction or hierarchy was planned is not reported in the registry record.

11. Confidence Intervals and Precision

A confidence interval gives a range of values compatible with the observed data under the assumptions of the calculation. It describes uncertainty about the estimated mean difference; it is not a range containing a stated proportion of individual participant scores. A narrower interval indicates greater statistical precision, while a wider interval leaves more uncertainty about the size and direction of the difference.

For the primary comparison, the mean difference is -1.9 and the unadjusted confidence interval runs from -4.064 to 0.264. Because the interval includes zero, the posted summary is compatible with no difference between group means as well as with differences in either direction. The unadjusted p-value is 0.085. Neither the p-value nor the interval identifies whether any difference is important to participants, and the registry record does not report a threshold for clinical importance.

The later anxiety comparison has a mean difference of -3.1 and an unadjusted interval from -5.487 to -0.713. This interval lies below zero, but it belongs to a secondary assessment and should be interpreted with that status in mind. Its apparent precision does not remove uncertainty about analysis choices, missing outcomes, or multiplicity.

Confidence intervals depend on the statistical model and assumptions used to calculate them. As a general point, if participants in the same intervention group have correlated outcomes, an analysis that treats every score as independent could misstate uncertainty. The registry record identifies a partially nested design but does not report how that dependence was handled in an inferential model. The posted intervals are therefore best read as unadjusted summary-based intervals, not as evidence that every design feature was incorporated.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations express sample size as participants per arm, not as total events. They are not observed power. The calculation assumptions listed with those illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each illustration uses a stated fraction of the observed effect as the effect to detect. The registry record does not report the original trial sample-size justification or its design assumptions.

The 80% power column represents the number of participants per arm that the planning calculation indicates would be needed for an 80% chance of detecting the specified effect under its assumptions, if that effect and model were correct. The 90% power column describes the corresponding planning target for a 90% chance. These are design-planning quantities, not probabilities that the trial result is correct and not a measure of the power actually achieved after the trial.

The rows consider planning for the full observed effect and for smaller fractions of that effect. A smaller target effect is harder to distinguish from random variation, so more participants per arm are needed to reach the same planned power. These figures are illustrations based on the observed estimate, not the trial’s own planned sample size. The registry record does not report the original rationale for enrollment or whether any other planning assumptions were used.

Such calculations are sensitive to the estimated effect, variability, allocation, analysis method, and design. In a partially nested study, the group structure may affect the amount of information contributed by participants, but the posted illustration uses the stated normal-approximation assumptions. It should not be read as a complete design calculation for a future trial without considering its specific structure and planned analysis.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -1.900; pooled standard deviation σ = 6.960.
2. n = 2 × (1.96 + 0.842)² × 6.960² / -1.900² = 210.6, rounded up to 211 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -1.9                      # observed difference in means
sigma <- 6.95994831181559                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4335279)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 211 (80% power), 282 (90% power)
 75% of observed effect: n per arm = 375 (80% power), 502 (90% power)
 50% of observed effect: n per arm = 843 (80% power), 1,128 (90% power)
power.t.test: 211.6 
Simulated power at n = 211 per arm: 0.802 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary anxiety endpoint and several secondary outcomes, including a later anxiety assessment. It does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a plan for controlling the overall false-positive risk across outcomes and time points. As a general statistical matter, testing multiple outcomes increases the chance that at least one comparison will appear statistically notable by chance. The unadjusted secondary p-value should therefore not be interpreted as if it were the only test conducted.

The record includes outcome counts for the primary assessment and for the later anxiety assessment, but it does not explain why the counts differ from enrollment or from one assessment to another. It does not report a missing-data approach, reasons for missing outcomes, imputation methods, or sensitivity analyses. Missing outcomes can affect both the estimate and its uncertainty, particularly if the probability of missingness is related to symptoms or treatment experience. Without the handling details, the direction or extent of any such influence cannot be determined.

The registry record does not report whether the primary analysis followed an intention-to-treat principle, whether participants were analyzed according to randomized assignment, or whether a different analysis population was used. It also does not report a detailed protocol for exclusions or adherence-based analyses. The outcome counts should therefore be read as the numbers contributing to the posted summaries, not as proof of a particular analysis population.

The design is described as partially nested, but the registry record does not report the model used to account for intervention-group clustering. It also does not describe covariate adjustment, baseline-score adjustment, or any planned repeated-measures analysis. These details matter because analysis choices influence standard errors, confidence intervals, and p-values. The numerical comparisons can be described as posted unadjusted summaries, while their relationship to the trial’s intended analysis plan remains unreported in the registry record.

15. 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 record lists 86 participants at risk in each group. For the SPIN-CHAT group, it records 0 serious adverse events, 0 other adverse events, and 0 deaths. For the wait-list control group, it likewise records 0 serious adverse events, 0 other adverse events, and 0 deaths. These figures describe the event counts recorded in the registry for the listed groups and risk populations.

Zero recorded events does not establish that no event occurred outside the recorded reporting period or that an intervention has no safety risks. It means that the registry record reports no events in those categories for the stated groups. Interpretation also depends on how events were defined, collected, and followed. The record does not provide detailed event definitions or narrative safety findings in the posted information. The adverse-event counts should be read as a report of recorded events, rather than as a general guarantee of safety.

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

The primary result describes average anxiety scores at 4-weeks post-randomization among participants with posted outcome data. The SPIN-CHAT group mean was 56.9 and the wait-list control mean was 58.8, with a mean difference of -1.9. The unadjusted confidence interval includes zero, and the unadjusted p-value is 0.085. These statistics indicate uncertainty about the size and direction of the primary between-group difference; they do not establish that the groups were identical.

The result also does not establish that the program caused a change in anxiety. Randomization supports causal comparison when the trial is analyzed according to an appropriate plan, but the registry record does not report the full analysis model, the handling of the partially nested design, the missing-data approach, or the analysis population. The posted summary comparison alone cannot resolve those methodological uncertainties.

The later anxiety assessment has an unadjusted mean difference of -3.1, with a confidence interval that lies below zero. It is a secondary result and occurs at a different time point. It should not be substituted for the primary endpoint, and it does not by itself show that the difference changed over time. The record does not report a direct analysis of change in the group difference between assessment times.

A statistically notable comparison is not automatically clinically important. The record does not report a threshold for meaningful change on the PROMIS Anxiety T-score, and a group average does not describe every participant’s response. Nor do the posted results establish applicability to all people with systemic sclerosis or to settings beyond the trial. They answer a narrower question about measured scores in this randomized study, at the recorded time points, under the limitations of the reported information.

17. Why This Trial Matters Statistically

This trial addresses a question that links an acute public-health context with mental health outcomes in a population described as vulnerable because of existing systemic sclerosis. The intervention used group videoconferencing during COVID-19 restrictions, and the primary outcome was a standardized self-reported anxiety measure. The trial therefore illustrates how a randomized design can evaluate a behavioral program when outcomes are continuous symptom scores rather than events or diagnoses.

Its partially nested structure is statistically important. Intervention participants were organized into training groups, so their responses may share influences. A sound analysis must consider the way outcomes are grouped, while recognizing that the control participants did not receive the same group intervention. The registry record identifies this design feature but does not report its analysis method, making the distinction between a simple summary comparison and a design-aware inference especially relevant.

The posted primary and later anxiety comparisons also illustrate why endpoints and time points need to be distinguished. The primary assessment has an interval that includes zero, while the secondary assessment’s interval lies below zero. Those summaries are not interchangeable: the latter does not rewrite the primary result, and multiple outcomes make unadjusted findings less conclusive. This is a useful example of interpreting a pattern without selecting only the most favorable time point.

Finally, the registry record offers group summaries but leaves important analysis details unreported, including the original sample-size justification, missing-data methods, multiplicity plan, and analysis population. Recognizing those limits is part of statistical interpretation. It helps separate what the observed summaries describe from what a full protocol-based analysis might establish.

18. 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 does not report the original sample-size rationale, detailed eligibility criteria, or the complete statistical analysis plan. It also does not provide the method used to account for the partially nested intervention groups. These omissions limit assessment of whether the reported uncertainty reflects the design and planned analysis appropriately.

Outcome counts vary across the primary and later anxiety assessments, and the record does not explain the differences or report how missing data were handled. Reasons for missing outcomes and sensitivity analyses are not reported in the registry record. The absence of those details makes it difficult to judge whether the posted group means represent comparable sets of randomized participants.

The record lists several secondary outcomes, but numerical summaries are not available for all of them in the posted results. It also does not report a multiplicity strategy. Consequently, the later anxiety result should be interpreted cautiously alongside the primary outcome rather than as a standalone confirmation.

The intervention description states the frequency and duration of the program but has incomplete text for session length. The record describes the trial as unmasked, and it does not report further detail on outcome collection or analysis masking. The posted information also does not identify a clinically important difference threshold for the anxiety scale. These limitations constrain conclusions about implementation, bias, and the practical meaning of the score differences.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Evaluation of the Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together Program — NCT04335279.
• Registry record last updated 2023-02-01; status last verified 2022-05.
• Results first posted 2023-02-01.
• 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.

22. Record Summary

The registry record describes a completed randomized, parallel-group, unmasked trial of the SPIN-CHAT videoconference program versus wait-list control among people with systemic sclerosis. Enrollment was 172. The primary endpoint was mean PROMIS Anxiety 4a v1.0 T-score at 4-weeks post-randomization.

The posted primary mean difference was -1.9, with an unadjusted confidence interval that includes zero and an unadjusted p-value of 0.085. The secondary anxiety comparison at 10-weeks post-randomization had a mean difference of -3.1 and an unadjusted p-value of 0.011. The registry record does not report the full statistical analysis plan, missing-data approach, or multiplicity handling, so the comparisons should be interpreted as posted summaries rather than a complete account of all trial analyses.