Study to Test the Safe and Effective Use of an e-Device for the Self-injection of Certolizumab Pegol Solution by Subjects With Moderate to Severe Active Rheumatoid Arthritis, Active Ankylosing Spondylitis, Active Psoriatic Arthritis, or Moderately to Severely Active Crohn's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Test the Safe and Effective Use of an e-Device for the Self-injection of Certolizumab Pegol Solution by Subjects With Moderate to Severe Active Rheumatoid Arthritis, Active Ankylosing Spondylitis, Active Psoriatic Arthritis, or Moderately to Severely Active Crohn's Disease (NCT03357471), a non-randomized phase 3 study. The primary outcome is Percentage of Subjects Able to Self-administer Safe and Effective Injections Using the e-Device at Visit 2.

2. Clinical Question

The study focused on the use of the injection device by people already familiar with self-injecting certolizumab pegol using prefilled syringes. It therefore asks a device-use question in that defined setting, rather than whether certolizumab pegol is effective for the listed conditions. The registry describes a phase 3 study sponsored by UCB Biopharma S.P.R.L. It reports enrollment of 70 and a completed status.

The primary endpoint combines dose delivery with device-related safety. A dose had to be judged complete by visual inspection of the cassette, and there could be no adverse event related to use of the e-Device that would preclude continued use for self-injection. For Q4W, both injections at the visit had to satisfy the criteria. The record does not report the percentage meeting this endpoint, its denominator, or its confidence interval, so the primary question cannot be answered from the recorded results.

3. Trial Design

The registry describes a multicenter, open-label, non-randomized, parallel phase 3 study. Its stated purpose was to evaluate whether subjects already prescribed certolizumab pegol and experienced with self-injection using prefilled syringes could safely and effectively use the e-Device. The study also planned visual examination of used devices and cassettes for structural integrity. Enrollment was 70. The record gives a start date of 2017-11-03, a primary completion date of 2018-07-02, and a completed status.

Two study arms used different dosing schedules. The Q2W arm involved self-injection of 200 mg every 2 weeks. The Q4W arm involved 400 mg every 4 weeks, administered as 2 x 200 mg injections. The registry identifies the study as parallel, but it does not describe randomized assignment. Because allocation was non-randomized and there was no masking, differences between arms should not be interpreted as if they arose from a randomized comparison. The record itself cautions that the arms are not a like-for-like control comparison.

The primary assessment took place at Visit 2: Week 2 for Q2W and Week 4 for Q4W. The primary population was the Safety Set, defined as subjects who received at least 1 dose of certolizumab pegol during the study through the e-Device. For the percentage calculation, the denominator was restricted to Safety Set subjects who participated in Visit 2 and received at least 1 dose. The record does not report further details about assignment procedures, site-level methods, or other analysis populations.

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: Participant Flow refers to the Safety Set (SS), which consisted of all subjects of the study who had received at least 1 dose of CZP during the study (e-Device).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety Set (SS) consisted of all subjects of the study who had received at least 1 dose of CZP during the study (e-Device). Percentages were based on the number of SS subjects that participated in Visit 2 and received at least 1 dose of CZP.

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: Baseline Characteristics refers to the Safety Set which consisted of all subjects who received at least 1 dose of CZP during the study (e-Device).

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Subjects Able to Self-administer Safe and Effective Injections Using the e-Device at Visit 2, measured over Visit 2 (Week 2 for Q2W; Week 4 for Q4W).

The primary endpoint is the percentage of subjects able to self-administer injections classified as safe and effective at Visit 2. The assessment required complete delivery of the certolizumab pegol dose, confirmed by visual inspection showing the prefilled syringe container to be empty, and no adverse event related to e-Device use that would preclude continued self-injection. The assessment was made by a healthcare provider.

For subjects on Q2W, the endpoint concerned the injection assessed at the Week 2 visit. For subjects on Q4W, two injections were given at a visit, and the endpoint was met only when both were judged safe and effective. Thus the Q4W subject-level result required success on each injection, not merely one of them.

A percentage is useful for expressing how commonly the device-use criteria were met in the assessed population. The endpoint combines a direct check of dose delivery with a device-related safety condition, so it is more specific than a general rating of ease of use. Its interpretation depends on the defined assessment, visit, and denominator. The registry record states that the endpoint was to be reported with a 90% confidence interval, but the observed percentage, denominator, and interval are not reported in the registry record. The endpoint definition alone therefore does not establish how often the criteria were met.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is this? The primary outcome is a binary classification for each assessed subject: the criteria were either met or not met. The registry expresses the group result as a percentage of subjects. In general, a percentage for a binary outcome is the count meeting the criterion divided by the defined denominator, then expressed as a proportion on a percentage scale. Here, the specified denominator is limited to Safety Set subjects who attended Visit 2 and received at least 1 dose. The record does not give the numerator or denominator actually used, or the resulting percentage.

What does the confidence interval contribute? The endpoint was specified with a 90% confidence interval. In general, a confidence interval describes the statistical uncertainty around an estimated quantity under the method used to calculate it. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. It is not a guarantee that the true value lies within the particular interval, and it does not remove possible bias from the study design or outcome assessment. Since neither the estimate nor its interval is reported in the registry record, precision cannot be evaluated for this endpoint.

Why does the endpoint definition matter? A percentage is interpretable only in relation to what qualifies as an event and who is counted in its denominator. The endpoint required confirmed complete dose delivery and no device-related adverse event that would preclude continued use. A subject failing either condition would not meet the combined definition. For the Q4W schedule, both injections had to meet the conditions. This rule makes the Q4W subject-level endpoint stricter than a definition that counted success if either injection met the criteria, but the record does not report outcome counts with which to quantify the consequence of that rule.

What can be inferred from the design? The study is identified as non-randomized, open-label, and parallel. In general, randomization helps balance measured and unmeasured characteristics between assigned groups, while masking can limit some forms of assessment or reporting bias. Neither feature is reported for this study. The registry also explicitly cautions that the arms are not a like-for-like control comparison. Consequently, a difference between arm summaries, if one were reported, would not by itself establish that the dosing schedule caused the difference. No adjusted comparison or statistical model is described in the registry record.

What are the planning assumptions? The record describes sample-size illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the planning target is expressed as a stated fraction of the observed effect. These are planning assumptions, not a report of the study's original design rationale. The record does not report a sample-size justification or the numerical results of the planning illustrations in the registry record for this analysis. A planning calculation is not observed power and does not establish that a study had a particular probability of detecting an effect.

In general, normal-approximation planning methods use an assumed effect and variability to estimate the sample size needed for a specified design. Their output depends on those assumptions and the planned analysis. It should not be confused with an estimate from the completed trial. In this record, there is no reported primary effect estimate to inspect, and the planning assumptions do not fill that gap. They also do not resolve limitations from non-random allocation, open-label assessment, or a missing outcome report.

What about safety counts? The adverse-event summaries distinguish subjects at risk from subjects reported as affected. The registry records zero affected for the serious and other adverse-event summaries in each listed group, along with zero deaths. In general, a count of zero in a study sample does not imply that the underlying event risk is zero. The precision of a risk estimate depends on the denominator and the statistical method, and no confidence intervals for these safety counts are reported. These counts should be read as the registry's reported observations, not as proof that device-related events cannot occur.

What is not described? The record does not report the method used to calculate the primary confidence interval, any hypothesis test for the endpoint, adjustment for baseline characteristics, or handling of missing observations. It also does not provide a full statistical analysis plan. These details would be needed to evaluate the analysis beyond the endpoint definition and stated planning assumptions. The statistical methods that can be described are therefore limited to the binary percentage endpoint, its specified 90% interval, the defined analysis population, and the planning assumptions recorded in the registry.

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("Certolizumab Pegol Q2W Injection by e-Device (SS)", "Certolizumab Pegol Q4W Injection by e-Device (SS)")
n      <- c(33, 32)
events <- c(33, 31)
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  Certolizumab Pegol Q2W Injection by e-Device (SS)  33  33  100.0  89.4  100.0  89.6  100.0  89.7  99.9
ARM  Certolizumab Pegol Q4W Injection by e-Device (SS)  32  31  96.9  83.8  99.9  84.3  99.4  84.2  99.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes. These include the percentage able to self-administer safe and effective injections at Visit 1, cassette structural integrity findings, changes in vital signs, and adverse events during the study. Listing multiple outcomes raises a general statistical issue: when many outcomes or comparisons are examined, the chance of at least one apparently notable finding can increase unless the analysis plan addresses multiplicity. The registry record does not report whether any multiplicity adjustment or outcome-testing hierarchy was planned.

The registry identifies the primary endpoint as a percentage with a 90% confidence interval, but does not report the estimate or interval. It records 10 outcome measures and 0 analyses. The available record does not give outcome-level results for the listed secondary measures, or an explanation of how results were selected or analyzed. An adjustment for multiple testing, if any, is not reported in the registry record.

Missing-data handling is also not reported in the registry record. The primary population is defined as Safety Set subjects who participated in Visit 2 and received at least 1 dose. This definition states who could contribute to the primary percentage, but it does not explain how subjects without a Visit 2 assessment were handled, whether any data were imputed, or whether sensitivity analyses were conducted. The record does not describe an intention-to-treat or per-protocol population for this endpoint.

These omissions limit assessment of the analysis, but they do not establish that a particular method was or was not used. The registry record does not report the relevant details. The primary result's absence also prevents assessment of its precision or of how missing observations may have influenced it.

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 5% reporting threshold.

The registry's adverse-event summary reports 35 subjects at risk and 0 affected by serious adverse events in the Q2W group. For the Q4W group, it reports 32 at risk and 0 affected. The reported counts for other adverse events are 0 in each group, and deaths are also recorded as 0 in each group.

These are counts in the reported safety groups, not estimates of risk for every person who might use the device. In general, observing zero affected subjects in a study does not prove that the event is impossible or that its underlying risk is zero. The size and definition of the safety population, the length of observation, and the event ascertainment process all inform interpretation. The registry does not report confidence intervals for these counts or further details about event timing and classification in the registry record for this analysis.

The serious adverse-event counts should also be kept distinct from the primary endpoint. The primary endpoint required complete dose delivery and no device-related adverse event that would preclude continued use. The registry's serious adverse-event summary is not a report of the percentage meeting that combined endpoint. It should not be used to infer that all injections were complete or that all subjects satisfied the primary criteria.

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

The study addresses a practical, defined question: whether people already using certolizumab pegol could self-inject it with an e-Device under specified assessment criteria. The registry defines complete dose delivery through visual inspection and adds a device-related safety condition. For Q4W, both injections had to pass. These details make the intended outcome more precise than a general statement about whether the device was acceptable.

However, the primary percentage, denominator, and 90% confidence interval are not reported in the registry record. The available record therefore cannot show how often the endpoint was met or how precisely that percentage was estimated. The serious and other adverse-event summaries report zero affected subjects in each arm, but those observations do not supply the primary outcome or demonstrate that the endpoint criteria were met.

The result, if available, would apply most directly to the study setting and population described: subjects already prescribed certolizumab pegol who had self-injected using prefilled syringes for at least the previous 3 months. The record includes several distinct conditions, and it does not report outcome estimates separately by condition in the registry record for this analysis. The findings therefore cannot be interpreted as condition-specific evidence from the reported information.

The design also constrains what could be concluded from any arm comparison. Allocation was non-randomized, masking was absent, and the registry cautions that the arms are not a like-for-like control comparison. A difference between dosing-schedule groups would not by itself establish a causal effect. Most importantly, the primary outcome result itself is absent, so the posted record does not support a quantitative conclusion about the frequency of safe and effective e-Device self-injection.

14. Why This Trial Matters Statistically

This trial is statistically notable for separating a device-use endpoint from a treatment-efficacy question. The primary measure asks whether subjects could deliver the prescribed dose with the e-Device and avoid a device-related event that would preclude continued use. It is a binary, operationally defined outcome rather than a measure of disease activity. That distinction matters when interpreting the study's purpose and any result that might be reported.

The endpoint also illustrates how the unit of success can depend on the dosing regimen. The Q4W schedule required both injections to meet the criteria for the subject to count as successful. A clear definition of this rule is essential for interpreting the resulting percentage and comparing it with a different endpoint definition. The actual percentage and confidence interval, however, are not reported in the registry record.

From a statistical perspective, the record also illustrates why a study's design and its uncertainty estimates need to be read together. A confidence interval can describe sampling uncertainty around an estimate, but it cannot correct for non-random allocation or make the two arms a valid control comparison. Here, the registry identifies the non-randomized design and explicitly cautions against a like-for-like interpretation. Its reported adverse-event counts are descriptive and do not substitute for the primary outcome.

Finally, the record demonstrates the limits of interpreting an outcome definition without an outcome estimate. The methods specify a percentage and a 90% confidence interval, but neither is reported. Statistical transparency requires both a clear definition of what was measured and the result needed to understand its frequency and precision. The record offers the former, while the latter is not reported in the registry record.

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 main limitation for interpreting the posted results is that the primary endpoint estimate, denominator, and 90% confidence interval are not reported in the registry record. Without them, the frequency and precision of meeting the safe-and-effective injection criteria cannot be assessed. The record also does not provide outcome-level results for the listed secondary measures in the registry record for this analysis.

The study population was already prescribed certolizumab pegol and had experience self-injecting with prefilled syringes for at least the previous 3 months. The record does not establish how device use would perform among people without that experience. The listed conditions are rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and Crohn's disease, but condition-specific endpoint results are not reported in the registry record.

The non-randomized, open-label design limits comparisons between the Q2W and Q4W arms. The registry explicitly cautions that the arms are not a like-for-like control comparison. It does not report methods for adjusting for group differences or for managing missing Visit 2 assessments. The primary assessment was also schedule-specific, occurring at Week 2 for Q2W and Week 4 for Q4W; the record does not provide results that would allow assessment across those visits.

The endpoint was based on healthcare-provider assessment and visual inspection of the cassette, while masking was absent. The registry does not describe additional procedures to reduce assessment bias. It also does not report the method used for the confidence interval, multiplicity handling, or a detailed statistical analysis plan. These items are not reported in the registry record and should not be inferred from the endpoint definition alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Test the Safe and Effective Use of an e-Device for the Self-injection of Certolizumab Pegol Solution by Subjects With Moderate to Severe Active Rheumatoid Arthritis, Active Ankylosing Spondylitis, Active Psoriatic Arthritis, or Moderately to Severely Active Crohn's Disease — NCT03357471.
• Registry record last updated 2019-10-25; status last verified 2019-10.
• Results first posted 2019-10-25.
• 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

NCT03357471 is a completed, multicenter, open-label, non-randomized, parallel phase 3 study sponsored by UCB Biopharma S.P.R.L. Enrollment was 70. The study assessed self-injection of certolizumab pegol with an electro-mechanical e-Device among subjects already prescribed the treatment and experienced with prefilled-syringe self-injection.

The primary endpoint was the percentage meeting criteria for safe and effective self-injection at Visit 2, assessed at Week 2 for Q2W and Week 4 for Q4W. The endpoint required complete dose delivery and no device-related adverse event that would preclude continued use; Q4W subjects had to meet the criteria for both injections. The primary result, denominator, and 90% confidence interval are not reported in the registry record.

The registry's safety summary records zero affected by serious or other adverse events and zero deaths in each listed group. The record cautions that the non-randomized arms are not a like-for-like control comparison.