A Study to Evaluate an Updated Dexamethasone Intravitreal (Into the Eye) Applicator in Adult Participants With Macular Edema Due to Diseases of the Retina: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate an Updated Dexamethasone Intravitreal (Into the Eye) Applicator in Adult Participants With Macular Edema Due to Diseases of the Retina (NCT04976777), a randomized phase 3 study. The primary outcome is Number of Participants Experiencing at Least One Adverse Events (AEs).

2. Clinical Question

The contrast is between delivery devices, not between different medicines: both groups received a dexamethasone implant. The stated study purpose was to evaluate the updated applicator in participants with macular edema due to retinal diseases. The primary endpoint is a count of participants with one or more adverse events, rather than a count of all events or a measure of visual function. The comparison therefore describes observed short-term adverse-event occurrence in the two groups. It does not by itself answer broader questions about longer-term outcomes, the implant’s efficacy, or whether the applicators are equivalent in every respect.

3. Trial Design

This was a Phase 3, randomized, open-label, parallel-group trial. The registry record reports enrollment of 54 participants. The posted outcome groups contain 36 participants assigned to the updated DEX PS DDS 0.7 mg applicator and 18 assigned to the approved DEX PS DDS 0.7 mg applicator. Both groups received a single intravitreal administration of the same implant on Day 1, followed by observation through Day 7.

The study summary describes an evaluation of the updated applicator, with the applicator function assessed through medical assessment, checks for side effects, procedural complications and product complaints, and evaluation of the administration procedure. The registry record identifies the primary outcome as the number of participants experiencing at least one adverse event up to 7 days after study drug administration. The posted primary endpoint population is described as the SAS, including participants who received the implant.

The study was sponsored by AbbVie. The registry record lists a start date of 2021-10-12, a primary completion date of 2022-02-09, and a status of completed. The study summary describes approximately 7-10 sites in the United States. The specific randomization procedure, allocation ratio as planned, masking procedures beyond the listed absence of masking, and original sample-size justification are not reported in the registry record. The registry record also does not report the protocol’s full visit schedule or any follow-up beyond Day 7 for this primary result.

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:

Analysis population for the primary outcome, as defined in the registry: SAS included of all participants who received DEX PS DDS Implant.

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: Safety Analysis Set (SAS) included of all participants who received DEX PS DDS Implant.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Experiencing at Least One Adverse Events (AEs), measured over Up to 7 Days After Study Drug Administration.

The primary endpoint is the number of participants experiencing at least one adverse event up to 7 days after study drug administration. An adverse event is defined in the registry record as an untoward medical occurrence in a participant administered a pharmaceutical product; it does not necessarily have a causal relationship with treatment. The investigator assesses each event’s relationship to study use.

The endpoint counts participants with one or more events, rather than counting each event separately. A participant with multiple events still contributes as a participant who experienced at least one adverse event for this measure. The posted results report 13 participants in the updated-applicator group and 7 in the approved-applicator group as having at least one event.

This measure is relevant to the study’s short-term evaluation because the stated aim concerns an updated delivery applicator, and the summary describes checking for side effects, procedural complications and product complaints. The count can capture whether participants experienced adverse events during the stated observation period, but it does not identify the cause of each event or establish that an event arose from the applicator. Nor does this endpoint, by itself, describe the nature, severity, duration, or clinical consequences of every event. Those details require other reported outcomes or event-level information, which are not included in this primary endpoint summary.

7. Results Posted in the Registry

• Approved DEX PS DDS 0.7 mg: 38.9% (7/18) versus 36.1% (13/36) on control; risk difference 2.8 percentage points (95% CI -24.7 to 30.2), risk ratio 1.08 (0.52–2.22); unadjusted two-proportion z-test p = 0.842.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant either experienced at least one adverse event during the stated period or did not. For this kind of outcome, the observed group proportions and a contrast between them provide a direct description of how frequently the event indicator occurred. The posted counts are 13 of 36 in the updated-applicator group and 7 of 18 in the approved-applicator group. These are the numbers of participants with an event and the group denominators reported for the primary outcome.

What does the risk difference express?

The risk difference is an absolute comparison of the two group proportions. In the posted result, it is oriented as the approved-applicator group minus the updated-applicator group and is 0.028. A positive value under this orientation means the observed proportion is higher in the approved-applicator group; a negative value would mean it is higher in the updated-applicator group. The estimate is a difference in proportions, not a relative increase and not a count of additional participants. General explanation: absolute differences can be useful because they describe the size of a contrast on the original probability scale.

How do relative measures differ?

The risk ratio compares the proportions by division, while the odds ratio compares the odds of the event between groups. The posted risk ratio is 1.077 and the posted odds ratio is 1.126. These measures use different scales from the risk difference, so their numerical values should not be compared as though they represented the same quantity. General explanation: when an outcome is not rare, the odds ratio can be farther from the no-difference value than a risk ratio; interpretation should therefore name the measure being used. The registry record does not report that the odds ratio was the primary comparison measure.

What does the confidence interval add?

A confidence interval gives a range of estimates compatible with the data under the method used, and communicates precision as well as direction. The risk-difference interval is -0.247 to 0.302. It includes zero, the value corresponding to no observed difference in proportions. The interval also includes values on either side of zero, so the result does not pin down the direction or size of the underlying difference precisely. General explanation: a confidence interval is not a guarantee that the true value lies in the reported range, and it is not a probability statement about a particular hypothesis.

What does the p-value describe?

The posted unadjusted p-value is 0.842. General explanation: a p-value describes how unusual data at least as discrepant as those observed would be under a specified null model and analysis procedure. It does not measure the probability that the null hypothesis is true, the probability that a treatment caused an event, or the probability that the findings will repeat. The registry record does not report the particular test used to obtain this p-value, so no specific test should be inferred from the result alone.

Why can the estimate be imprecise?

General explanation: estimates based on limited information can vary substantially from one sample to another. The posted groups contain 36 and 18 participants, and the interval around the risk difference is broad. The randomized design supports a planned comparison, but randomization does not remove sampling uncertainty. A numerical point estimate should therefore be considered together with its interval and with the limits of the endpoint’s follow-up period.

The study’s primary endpoint population is described as the SAS, including participants who received the implant. The registry record does not report whether all randomized participants were included in every analysis, how missing outcome data were handled, or whether any adjustments were made. No adjusted comparison is identified in the posted results. The values therefore support interpretation of the posted unadjusted group comparison, but do not establish what other analysis choices were prespecified or performed.

10. Confidence Intervals and Precision

The risk-difference estimate is 0.028 for approved minus updated, with a 95% confidence interval from -0.247 to 0.302. This interval crosses zero, so the posted data are compatible with no difference as well as with a difference in either direction. Its breadth signals limited precision: the point estimate alone should not be treated as a precise measure of the contrast.

The relative estimates are also uncertain. The risk ratio is 1.077, with a 95% confidence interval from 0.522 to 2.221; the odds ratio is 1.126, with a 95% confidence interval from 0.351 to 3.615. Each interval includes its no-difference value. These estimates are expressed on different scales, but both convey uncertainty about the size and direction of the between-group contrast.

General explanation: a confidence interval reflects both the observed data and the statistical method used to construct it. A broad interval means that the data do not distinguish well among multiple plausible effect sizes. It is not evidence that all values in the interval are equally likely, and it does not establish equivalence merely because the interval includes zero. The registry record does not report a clinically acceptable margin for equivalence or noninferiority.

The primary endpoint was assessed up to 7 days after administration. Thus, these intervals quantify uncertainty for the posted short-term adverse-event comparison, not for longer-term safety, efficacy, or applicator performance. Precision for those other questions is not reported in the registry record.

11. 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 sample-size figures are planning illustrations based on the observed effect, not the trial’s original design justification. The registry record does not report the original sample-size assumptions. The illustrations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The figures are participants per arm for 80% power and participants per arm for 90% power. They are not total events, because this is not a time-to-event outcome.

The 80% power column gives a planning estimate of the number of participants in each arm under the stated assumptions for a design intended to have 80% probability of detecting the assumed effect at the specified significance level, if that effect were the true one and the assumptions held. The 90% column gives the corresponding planning estimate for 90% probability. These are design targets, not properties measured after a study is completed.

For 100% of the observed effect, the illustrations list 4,768 participants per arm for 80% power and 6,382 for 90% power. Planning for 75% of the observed effect lists 8,444 participants per arm for 80% power and 11,304 for 90% power. Planning for 50% of the observed effect lists 18,927 participants per arm for 80% power and 25,337 for 90% power. Smaller effects require more participants to distinguish them from no difference under otherwise similar assumptions.

These are planning illustrations, not observed power. The effect used is estimated from this trial’s posted results, so the illustrations depend on that estimate and should not be mistaken for a design recommendation or a report of the trial’s actual power.

12. 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 = 0.361; treatment proportion p₁ = 0.389; average p̄ = 0.375.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6847 = 1.3419.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6844 = 0.5760.
4. n = (1.3419 + 0.5760)² / (0.0278)² = 4,767.0, rounded up to 4,768 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 <- 0.361111111111111                          # control proportion
p1 <- 0.388888888888889                          # 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(4976777)
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 = 4,768 (80% power), 6,382 (90% power)
 75% of observed effect: n per arm = 8,444 (80% power), 11,304 (90% power)
 50% of observed effect: n per arm = 18,927 (80% power), 25,337 (90% power)
power.prop.test: 4767 
Simulated power at n = 4,768 per arm: 0.801 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry record reports two outcome measures and no posted secondary outcomes in the results summarized for this analysis. It also reports no posted analyses. The primary endpoint is the number of participants experiencing at least one adverse event, and the posted comparison includes an unadjusted p-value. The registry record does not report a broader multiplicity strategy, such as how testing across endpoints or analyses was handled.

Multiplicity matters in general when several hypotheses are tested: the chance of obtaining at least one apparently notable result can increase as the number of tests grows. That general concern cannot be quantified for this trial from the posted record, because the testing plan and any adjustment procedure are not reported. The presence of one posted primary comparison does not establish whether additional analyses were planned or performed outside the posted results.

The endpoint population is described as the SAS, including participants who received the DEX PS DDS implant. The registry record does not report a more detailed definition of this analysis population or whether the analysis followed assignment regardless of treatment received. It does not report participant flow, missing-outcome counts, an imputation method, or sensitivity analyses addressing missing data. No assumptions about those matters should be inferred from the group counts alone.

The record also does not report interim analyses, stopping rules, covariate adjustment, or the exact statistical test underlying the unadjusted p-value. These omissions limit assessment of whether the posted comparison follows a prespecified analysis plan and how robust it might be to alternative analysis decisions. The reported result remains interpretable as the posted comparison of observed participant counts, but those additional design and analysis details are not reported in the registry record.

14. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: covid-19 pneumonia (2.8%), chronic kidney disease (2.8%), renal failure (2.8%).

The serious adverse event summary reports 1 participant affected in the updated-applicator group and 0 in the approved-applicator group. The corresponding group sizes at risk are 36 and 18. The summary reports 11 participants with other adverse events in the updated-applicator group and 7 in the approved-applicator group. Deaths are reported as 0 in each group.

The registry record lists COVID-19 PNEUMONIA, CHRONIC KIDNEY DISEASE, and RENAL FAILURE among the top serious adverse event terms, each with 2.8%. The record does not clarify in the information summarized for this result how those term percentages map to participants or event counts, so they should be read as registry-listed terms and percentages rather than interpreted as additional group-specific rates.

These safety summaries describe events recorded during the study; they do not establish that an event was caused by the applicator or implant. The adverse-event definition explicitly allows events without a causal relationship to treatment. The observation period for the primary outcome was up to 7 days after administration, so the figures do not describe longer-term event occurrence. With the reported group sizes and short follow-up, counts should be interpreted descriptively and not as proof of a difference or absence of risk.

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

The primary result describes how often participants in each applicator group experienced at least one adverse event during follow-up through Day 7. The observed counts were 13 of 36 with the updated applicator and 7 of 18 with the approved applicator. The posted risk difference, defined as approved minus updated, is 0.028; its 95% confidence interval ranges from -0.247 to 0.302. The unadjusted p-value is 0.842. Together, these statistics show that the posted estimate is uncertain and that the data do not establish a clear difference in this endpoint.

That interpretation is narrower than saying the applicators are the same. A result that does not show a clear difference is not an equivalence finding. Establishing equivalence would require a prespecified margin and an analysis designed to assess whether the uncertainty lies within that margin; those details are not reported in the registry record. The wide confidence interval is especially important because it includes differences in both directions.

The endpoint is not a measure of whether dexamethasone improves macular edema. Both groups received the same implant, and the contrast concerns the applicator used to administer it. The adverse-event definition also does not require a causal link to treatment, so the counts cannot identify whether events were caused by the device, the implant, the administration procedure, or other circumstances.

Finally, the reported observation period is short, and the primary endpoint is a participant-level indicator of at least one event. The results do not describe long-term safety, event severity and duration in full, visual outcomes, or applicator performance across other settings. Those conclusions are not established by this posted comparison.

16. Why This Trial Matters Statistically

This trial poses a focused statistical question: whether short-term adverse-event occurrence differs between two applicators used to deliver the same dexamethasone implant. Separating the delivery device from the medicine is important to the interpretation of the comparison. The posted endpoint is a participant-level safety count, while the study summary also describes assessment of applicator function, procedural complications, and product complaints.

The randomized parallel-group design gives a structured basis for comparing the groups, but the size and uncertainty of the observed contrast still matter. The risk-difference interval ranges from -0.247 to 0.302, and the relative-measure intervals are also broad. This makes the trial a useful illustration of why a point estimate and p-value should not be read in isolation. The absence of a clearly separated estimate is not proof of equivalence, especially when the range of compatible differences is wide.

The trial also highlights how the endpoint definition shapes the question answered. Counting participants with at least one adverse event is straightforward to interpret as an occurrence measure, but it does not describe every event or establish causation. The short follow-up further limits the scope of the conclusion to the early period after administration.

For clinical researchers, the record demonstrates the value of reporting analysis populations, missing-data procedures, multiplicity decisions, and design assumptions alongside results. Those details are not reported in the registry record for this comparison. Their absence does not invalidate the posted counts, but it narrows the ability to evaluate the complete analysis strategy and to distinguish a descriptive result from a fully documented confirmatory analysis.

17. 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 primary endpoint covers adverse events up to 7 days after administration. This short observation window cannot describe later events, and the primary result does not establish longer-term safety or efficacy. The endpoint counts participants with at least one adverse event, so it does not by itself summarize the number of events per participant, event duration, or the full clinical course of each event.

The study is open-label, with no masking reported. The registry record does not state whether any outcome assessment was blinded or whether procedures were used to reduce the effect of knowledge of assignment on event reporting or assessment. The endpoint includes investigator assessment of an event’s relationship to study use, but the primary count includes adverse events whether or not a causal relationship is established.

The posted group sizes are 36 for the updated-applicator group and 18 for the approved-applicator group. The risk-difference confidence interval is broad, so the estimate does not tightly identify the size or direction of a possible difference. The registry record does not report the planned allocation ratio or the reason for the observed group-size distribution.

Additional limitations arise from missing reporting detail. The registry record does not report how missing outcome data were handled, the exact statistical test, an adjustment plan, interim analyses, or the original sample-size justification. It also does not provide posted secondary outcomes for this result. These omissions limit assessment of the full analysis plan and do not permit conclusions about other outcomes or longer-term comparisons.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Study to Evaluate an Updated Dexamethasone Intravitreal (Into the Eye) Applicator in Adult Participants With Macular Edema Due to Diseases of the Retina — NCT04976777.
• Registry record last updated 2023-02-28; status last verified 2023-02.
• Results first posted 2023-02-28.
• 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.

21. Record Summary

The registry record identifies NCT04976777 as a completed Phase 3 randomized, open-label, parallel-group study sponsored by AbbVie. It evaluated an updated DEX PS DDS applicator against the currently approved applicator in adult participants with macular edema due to retinal diseases. Both groups received a DEX PS DDS 0.7 mg implant, administered intravitreally on Day 1, with follow-up through Day 7.

The primary outcome was the number of participants experiencing at least one adverse event up to 7 days after administration. The posted group counts were 13 of 36 with the updated applicator and 7 of 18 with the approved applicator. The risk difference was 0.028 for approved minus updated, with a 95% confidence interval from -0.247 to 0.302 and an unadjusted p-value of 0.842. The registry record lists a start date of 2021-10-12 and primary completion date of 2022-02-09.