Impact of Therapeutic Patient Education on the Toxicity of Immune Checkpoint Inhibitors in Oncology: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Impact of Therapeutic Patient Education on the Toxicity of Immune Checkpoint Inhibitors in Oncology (NCT03948724), a randomized na study. The primary outcome is Proportion of Participants With at Least One Grade ≥3 Immune-related Adverse Event (irAE) (CTCAE v5.0) Within 25 Weeks After Initiation of Immune Checkpoint Inhibitor (ICI) Treatment.

2. Clinical Question

The question concerns whether the education program is associated with a difference in the occurrence of a severe immune-related adverse event over a specified period. It does not ask whether education changes every adverse event, whether it changes the timing or severity of events below Grade 3, or whether it affects outcomes beyond the posted follow-up period.

The primary outcome is a participant-level binary measure: each participant is classified according to whether at least one qualifying event occurred during the period. The posted results compare the two randomized groups. The record also lists secondary measures of injections received, anxiety, depression, and global health status or quality of life. Those outcomes address other aspects of treatment experience, but they do not replace the primary safety question.

3. Trial Design

The registry describes a randomized, parallel-group trial with no masking. The intervention groups were therapeutic patient education and standard care. Participants assigned to education were to receive 5 sessions; the standard-care description refers to usual information. The registry lists the sponsor as Institut Cancerologie de l'Ouest and the phase as NA.

The record lists enrollment of 412. For the primary outcome, the posted group summaries are 24 events among 272 participants in the education group and 15 among 133 participants in standard care. These outcome denominators are not the same as the registry enrollment figure. The record does not explain the relationship between those figures, so they should be read as distinct registry entries rather than reconciled by assumption.

The primary outcome covers the 25 weeks following initiation of immune checkpoint inhibitor treatment and uses CTCAE version 5.0 to define Grade 3 or higher immune-related adverse events. Secondary outcomes are described over 12 months. The record lists outcomes for injections received, HADS-A anxiety, EORTC QLQ-C30 global health status or quality of life, and depression assessed by HADS-A.

The registry status is completed. The listed start date is 2019-12-11 and the primary completion date is 2023-08-04. The record does not report the original sample-size justification, detailed randomization procedures, or the trial's analysis plan. No masking was used, so participants and relevant trial personnel were not blinded according to the registry entry.

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 Proportion of Participants With at Least One Grade ≥3 Immune-related Adverse Event (irAE) (CTCAE v5.0) Within 25 Weeks After Initiation of Immune Checkpoint Inhibitor (ICI) Treatment, measured over 25 weeks.

The primary endpoint is the proportion of participants with at least one immune-related adverse event of Grade 3 or higher during the 25 weeks after starting immune checkpoint inhibitor treatment. The event grade is defined using CTCAE version 5.0. The outcome is recorded at the participant level: the measure counts participants who experienced one or more qualifying events, rather than counting every event or measuring the duration of an event.

This endpoint is used to compare the frequency of serious toxicity between the education and standard-care groups over a defined follow-up period. Defining the outcome in advance by severity and time window gives the comparison a specific clinical and statistical target. It also means the result does not describe all immune-related adverse events: events below Grade 3 are outside the primary definition, and the measure does not distinguish participants with one qualifying event from those with multiple qualifying events.

The posted results report 24 participants with an event in the therapeutic patient education group and 15 in standard care. The registry's comparison expresses the difference as education minus standard care. That estimated risk difference is -0.025, with a 95% confidence interval from -0.088 to 0.039. The interval includes the no-difference value, so the estimate is not precise enough to rule out either a lower or a higher event proportion in the education group.

7. Results Posted in the Registry

• Therapeutic Patient Education: 8.8% (24/272) versus 11.3% (15/133) on control; risk difference -2.5 percentage points (95% CI -8.8 to 3.9), risk ratio 0.78 (0.42–1.44); unadjusted two-proportion z-test p = 0.432.

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.

Number of Immune Checkpoint Inhibitor (ICI) Injections Received During the Study Period

• 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:
  • Therapeutic Patient Education: mean 9.10 versus 8.90 on control; difference 0.20 (95% CI -0.68 to 1.08), standardized effect d = 0.05; z-test p = 0.655.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Therapeutic Patient Education and the control. The interval gives the range of effects that remain compatible with the data.

Anxiety Level Assessed by the Hospital Anxiety and Depression Scale (HADS-A)

• 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:
  • Therapeutic Patient Education: mean 4.80 versus 5.10 on control; difference -0.30 (95% CI -1.29 to 0.69), standardized effect d = -0.09; z-test p = 0.552.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Therapeutic Patient Education and the control. The interval gives the range of effects that remain compatible with the data.

Global Health Status/Quality of Life Assessed by Thethe European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Questionnaire

• 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:
  • Therapeutic Patient Education: mean 70.80 versus 64.80 on control; difference 6.00 (95% CI 0.06 to 11.94), standardized effect d = 0.29; z-test p = 0.048.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Therapeutic Patient Education than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes cover treatment exposure, anxiety, depression, and global health status or quality of life. Across these measures, the posted estimates do not form a uniformly clear pattern of differences between groups. The registry lists four posted secondary outcomes, while the primary endpoint addresses severe immune-related adverse events. The secondary measures provide context about other aspects of the treatment period, but they answer different questions from the primary safety endpoint.

These outcomes should be considered alongside, not as substitutes for, the primary result. A secondary measure can show a different pattern without resolving the uncertainty around severe immune-related adverse events. Similarly, the primary comparison does not determine the results for quality of life, anxiety, depression, or treatment exposure. Each outcome has its own measure, follow-up context, and available observations.

The record reports unadjusted secondary comparisons and no reported analyses. It also does not report a multiplicity adjustment or a prespecified hierarchy for interpreting multiple outcomes. When several outcomes are assessed, chance variation can produce a result that appears notable even if there is no underlying difference. This general issue reduces the weight that should be placed on an isolated secondary finding, particularly when its analysis plan and relationship to other outcomes are not described.

Accordingly, the secondary results are best treated as exploratory context in the registry record, not as independent confirmation of the primary comparison. They may motivate further study, but the record does not document enough about outcome selection, missing observations, or multiplicity handling to support strong conclusions from individual secondary p-values.

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

• Number of Immune Checkpoint Inhibitor (ICI) Injections Received During the Study Period
• Anxiety Level Assessed by the Hospital Anxiety and Depression Scale (HADS-A)
• Global Health Status/Quality of Life Assessed by Thethe European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Questionnaire
• Depressionlevel Assessed by the Hospital Anxiety and Depression Scale (HADS-A)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary because each participant is classified as having at least one qualifying event or not having one. The registry reports event counts and group denominators, then compares the proportions between the randomized groups. This makes the risk difference a natural measure: it expresses how far apart the two event proportions are on an absolute scale. The reported difference is calculated in the direction of therapeutic patient education minus standard care.

What does the risk difference express?

A risk difference compares event proportions by subtraction. A negative value means the proportion is lower in the first named group, while a positive value means it is higher. The observed estimate is -0.025, so its direction favors a lower observed event proportion in the education group. The estimate is a sample result, not a guarantee that the same difference would occur in another study or population.

The risk ratio and odds ratio describe relative rather than absolute contrasts. A risk ratio compares the event proportions directly; an odds ratio compares the odds of an event. These measures can be useful complements, but their interpretation differs from the risk difference. The registry reports a risk ratio of 0.782 with a confidence interval from 0.425 to 1.441, and an odds ratio of 0.761 with a confidence interval from 0.385 to 1.505. Their intervals include the no-association value, indicating uncertainty about the relative contrast as well.

How should the confidence interval be read?

A confidence interval describes the precision of an estimate under the statistical method used: narrower intervals indicate greater precision, while wider intervals indicate more uncertainty. It is not a range containing every plausible individual outcome, and it does not say that a particular value is the probability that the true effect has a particular location. For the primary risk difference, the interval runs from -0.088 to 0.039. Because it spans the no-difference value, the data are compatible with effects in both directions.

The unadjusted p-value for the primary comparison is 0.432. In general, a p-value measures how unusual the observed data, or data more extreme, would be under a specified no-difference model and its assumptions. It is not the probability that the null hypothesis is true, nor a measure of the size or clinical importance of an effect. The registry does not report an adjusted primary analysis or additional details of the method used to obtain this p-value.

What does unadjusted mean in these comparisons?

An unadjusted comparison uses the posted group summaries without accounting for other variables in a statistical model. Randomization is intended to support a fair comparison, but the registry record does not describe baseline characteristics or report adjusted estimates. Without those details, readers cannot assess whether the posted comparison included covariate adjustment or how any missing outcome data were handled. The posted comparison should therefore be understood as the unadjusted summary reported in the record, not as a fully documented account of the trial's analysis.

The endpoint uses participant counts, so it focuses on whether an event occurred rather than the number of events per participant. For count outcomes, over-dispersion can matter when observations vary more than a simple count model expects; that issue is not the basis of this primary endpoint because the posted primary measure is the count of participants with an event. This distinction also explains why its interpretation differs from the secondary measure of injections received, which is reported as a mean with a standard deviation.

How do the secondary comparisons differ?

The secondary outcomes include continuous measures summarized by group means and standard deviations. Their mean differences express the average score or count difference between groups. A confidence interval for a mean difference conveys uncertainty in that contrast, while the standard deviation describes variation among observations within a group. These are different quantities: a larger standard deviation does not by itself indicate a larger difference between group averages.

The record lists no reported analyses for the secondary outcomes. The posted mean comparisons should consequently be read as unadjusted summaries rather than results from a documented adjusted model. The record also does not report a multiplicity procedure for testing several outcomes. When several outcomes are examined, the chance of finding an apparently notable result among them can increase; this is a general statistical concern, not evidence that any particular posted result is false.

There is no indication in the record of a discrepancy between a sponsor analysis and the posted recalculations. The estimates and intervals can therefore be described as the posted statistical comparisons without an identified conflicting sponsor result. The registry record does not provide a more detailed prespecified statistical analysis plan, including how the investigators intended to address missing observations, protocol deviations, or multiple testing.

11. Confidence Intervals and Precision

The primary risk-difference estimate is -0.025, with a 95% confidence interval from -0.088 to 0.039. This interval is broad relative to the point estimate and crosses the no-difference value. It therefore allows for a lower event proportion in the education group as well as a higher one. The estimate points toward fewer events in the education group, but its precision does not establish that direction.

The relative measures also show appreciable uncertainty. The risk ratio is 0.782, with an interval from 0.425 to 1.441; the odds ratio is 0.761, with an interval from 0.385 to 1.505. The ranges include the no-association value, so they do not resolve whether the relative event frequency was lower or higher with education.

For continuous secondary outcomes, the interval width likewise matters alongside the mean difference. The posted comparisons include intervals both spanning and not spanning the no-difference value, but no adjusted analyses are reported. In general, an interval that only narrowly excludes the no-difference value still warrants attention to its width, the study context, and the number of outcomes examined. Statistical precision is not the same as clinical importance.

The registry record does not report a precision target or a formal sample-size justification for the trial's original design. The planning estimates based on observed effects are separate illustrations and do not establish the precision the trial was designed to achieve. Taken together, the primary interval indicates that the posted data leave substantial uncertainty about the size and direction of the effect.

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 figures are expressed as participants per arm, not as total participants or total events. They use the observed effect as a reference and show illustrative requirements for detecting the full observed effect, 75% of the observed effect, or 50% of the observed effect. The calculation assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The trial's own original design assumptions are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm under which the assumed effect would be detected in 80% of repeated studies, if the stated assumptions and effect were correct. The 90% power column uses a higher probability of detection and therefore generally calls for more participants per arm. For the primary outcome, the estimates range from 2,355 participants per arm for planning around 100% of the observed effect at 80% power to 13,290 participants per arm for planning around 50% of the observed effect at 90% power.

Smaller effects are harder to distinguish from random variation, so planning for a smaller fraction of the observed effect requires more participants. These figures are planning illustrations, not observed power. They do not show the probability that the completed trial's result is correct, and they are not evidence that the original trial was designed using these assumptions. The record's own sample-size justification is not reported in the registry record.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.113; treatment proportion p₁ = 0.088; average p̄ = 0.101.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4252 = 0.8334.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4249 = 0.3576.
4. n = (0.8334 + 0.3576)² / (-0.0245)² = 2,354.2, rounded up to 2,355 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
p0 <- 0.112781954887218                          # control proportion
p1 <- 0.0882352941176471                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(3948724)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 2,355 (80% power), 3,152 (90% power)
 75% of observed effect: n per arm = 4,300 (80% power), 5,755 (90% power)
 50% of observed effect: n per arm = 9,928 (80% power), 13,290 (90% power)
power.prop.test: 2354.2 
Simulated power at n = 2,355 per arm: 0.800 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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 lists a primary outcome and multiple secondary outcomes, but it does not report how the analysis addressed multiplicity. Multiplicity arises when several hypotheses are tested: even if no real differences exist, a collection of tests can produce an apparently notable result by chance. A prespecified hierarchy, adjustment procedure, or clear distinction between confirmatory and exploratory outcomes can help readers interpret such results. Those details are not reported in the registry record.

The record lists 5 outcome measures and 0 reported analyses. It includes posted comparisons for the primary outcome and several secondary outcomes, but it does not describe a complete statistical analysis plan. In particular, the registry record does not report whether outcomes were analyzed according to a prespecified hierarchy, whether multiplicity adjustments were planned, or whether any analyses were selected after examining the data.

Missing-data handling is also not reported in the registry record. The group denominators differ across outcomes, but the record does not explain why observations are unavailable for some measures, how missingness was defined, or whether any imputation or sensitivity analysis was performed. Without those details, it is not possible to determine how missing outcomes may have affected the estimates.

The analysis population is not reported in the registry record. The record does not specify whether participants were analyzed according to randomized assignment, whether exclusions occurred, or how treatment discontinuation and protocol deviations were handled. These matters are important because the interpretation of a randomized comparison depends partly on preserving the comparison created by random assignment. The available registry summaries do not permit a fuller assessment of those choices.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for both groups. In therapeutic patient education, 0 serious adverse events were reported among 275 participants at risk; in standard care, 0 were reported among 137 participants at risk. The record also reports 4 deaths in each group. These are separate reported safety counts and should not be assumed to be mutually exclusive or to describe the cause of death.

The figures describe the safety information entered in the registry; they do not establish that no serious events of any kind occurred outside the categories or reporting process represented in these entries. The record lists no top serious adverse-event terms. It does report other adverse events: 81 in the education group and 34 in standard care. The registry does not provide further detail in these entries about event type, severity, relatedness, or timing.

These safety summaries do not replace the primary endpoint, which has a specific definition, grading threshold, and follow-up window. The record does not explain how the safety counts relate to the primary outcome counts, so they should be read as separate registry measures.

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

The primary point estimate is in the direction of a lower proportion of participants with a Grade 3 or higher immune-related adverse event in the therapeutic patient education group. The estimated risk difference is -0.025. Its 95% confidence interval, from -0.088 to 0.039, includes the no-difference value, and the unadjusted p-value is 0.432. The posted results therefore do not establish a difference between groups, while also not ruling out potentially different effects in either direction.

This result does not demonstrate that education prevents severe immune-related adverse events, and it does not demonstrate that education has no effect. A non-significant comparison is not proof of equivalence. The interval communicates the key uncertainty: effects below and above no difference remain compatible with the data under the analysis represented by the estimate.

The endpoint is limited to at least one event of Grade 3 or higher during the 25 weeks after treatment initiation. It does not capture all forms of toxicity, events below that grade, the number of events per participant, or outcomes beyond that timeframe. The secondary outcomes address other measures over 12 months, but their unadjusted results and unreported multiplicity plan limit the strength of conclusions from individual findings.

The randomized design supports a comparison between assigned groups, but the registry record does not provide details of the analysis population, missing-data procedures, baseline characteristics, or a complete statistical plan. Those omissions constrain interpretation of the posted summaries. The results should be understood as registry-reported group comparisons, not as a complete account of every analysis or as a basis for individual treatment decisions.

17. Why This Trial Matters Statistically

This trial raises a useful statistical question about how a behavioral intervention is evaluated alongside a treatment whose toxicity is measured as a clinical event. The primary outcome is defined by participant-level occurrence, severity threshold, and a specified post-initiation period. That clarity helps readers distinguish the target outcome from broader concepts such as overall toxicity or treatment experience.

The comparison also illustrates why effect estimates and confidence intervals matter together. The observed risk difference favors education, but the confidence interval includes no difference and extends in both directions. Reporting the estimate alone could make the result appear more conclusive than it is; reporting only a p-value would hide the range of effects still compatible with the data.

The registry includes secondary outcomes spanning treatment exposure and patient-reported measures. Considering them can broaden the picture of what an education program might affect, but multiple outcomes also create interpretive challenges. Without a reported multiplicity plan and analysis population, it is important to distinguish descriptive patterns from confirmatory conclusions.

Finally, the planning illustrations make an important distinction between the effect observed in a completed study and the assumptions needed for a future design. They show how desired power and the size of the effect targeted affect planning requirements, but they do not reveal the original rationale for this trial. Clear reporting of those design and analysis decisions would help readers judge how the completed study was intended to answer its clinical question.

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 leaves several trial-specific questions unanswered. Although the trial is described as randomized, the method used to generate the allocation sequence and conceal assignment is not reported in the registry record. Masking is listed as none; the record does not explain whether outcome assessment was independently blinded or how lack of masking was considered in evaluating outcomes.

The primary outcome summaries use group denominators that differ from the registry enrollment figure. The record does not explain participant flow, reasons for exclusion, or whether all randomized participants were included in the endpoint analysis. The analysis population and missing-data procedures are not reported in the registry record, limiting assessment of how incomplete outcome information could affect the comparison.

The record does not report baseline group characteristics, adherence to the education sessions, or the statistical method in enough detail to assess potential imbalances or implementation differences. The original sample-size justification and a complete analysis plan are also not reported in the registry record. As a result, the planning illustrations based on observed effects should not be mistaken for the trial's design rationale.

The primary outcome is restricted to Grade 3 or higher events during 25 weeks, whereas the secondary measures have a 12-month timeframe. The registry does not explain how outcome ascertainment was conducted or whether event classifications were independently reviewed. The record also does not report a multiplicity strategy for the secondary outcomes. These limitations affect how confidently the posted summaries can be generalized beyond the specific measures and periods recorded.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Impact of Therapeutic Patient Education on the Toxicity of Immune Checkpoint Inhibitors in Oncology — NCT03948724.
• Registry record last updated 2026-08-31; status last verified 2026-05.
• Results first posted 2026-08-31.
• 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 describes a completed, randomized, parallel-group trial without masking, comparing therapeutic patient education with standard care among people receiving immune checkpoint inhibitors. The education program was described as 5 sessions, and standard care as usual information. Registry enrollment was 412.

The primary outcome was at least one Grade 3 or higher immune-related adverse event within 25 weeks of treatment initiation. The posted risk difference was -0.025, with a 95% confidence interval from -0.088 to 0.039 and an unadjusted p-value of 0.432. The estimate favors education, but the interval includes no difference.

The registry lists secondary outcomes for injections received, anxiety, depression, and global health status or quality of life, with a 12-month timeframe. No analyses are listed in the record. The original sample-size justification, analysis population, missing-data handling, and multiplicity plan are not reported in the registry record.