Bilateral Transversus Abdominis Plane Block With Exparel Verus Continuous Epidural Analgesia With Bupivacaine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bilateral Transversus Abdominis Plane Block With Exparel Verus Continuous Epidural Analgesia With Bupivacaine (NCT02996227), a randomized na study. The primary outcome is VRS Pain Score.

2. Clinical Question

3. Trial Design

The registry describes a randomized, controlled, parallel-group trial with no masking. Participants were allocated to bilateral TAP block with Exparel or epidural analgesia with bupivacaine. The record lists the trial as completed and reports enrollment of 514. It identifies major abdominal surgery and postoperative pain as the relevant clinical context. The trial's phase is listed as not applicable.

The primary outcome was a continuous measure: average VRS pain score over the first 72 postoperative hours. The outcome description says VRS was recorded every 4 hours for 72 hours after discharge from the post-anesthesia care unit (PACU), with summary statistics reported as means and standard deviations of average pain during the first 72 postoperative hours. The record notes two missing primary outcomes in the epidural group because surgery was cancelled.

For the primary outcome, the reported group summaries are 4.3 with a standard deviation of 1.8 for TAP block with Exparel and 4.2 with a standard deviation of 1.8 for epidural analgesia with bupivacaine. The corresponding listed group sizes are 255 and 241. The sponsor's primary analysis is described as a mixed models analysis of final values and is categorized as non-inferiority. The registry does not report the non-inferiority margin or the original sample-size justification.

Other listed outcomes include cumulative duration of activity, opioid-related side effects, hemodynamic instability, quality of recovery after anesthesia, and length of hospital stay. The record does not report enough detail about the protocol, allocation procedures, or analysis populations to establish how every outcome was collected or analyzed.

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

Analysis population for the primary outcome, as defined in the registry: Two patients had missing outcomes due to the cancellation of surgery in Epidural analgesia with Bupivacaine group.

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 VRS Pain Score, measured over The Verbal Response Scale was recorded every 4 hours for 72 hours after discharge from the PACU..

The primary endpoint is the average pain score measured with the Verbal Response Scale (VRS). The scale ranges from 0, meaning no pain, to 10, meaning the worst pain ever experienced. The record says scores were recorded every 4 hours for 72 hours after discharge from the PACU; the reported summary is the mean and standard deviation of average pain during the first 72 postoperative hours.

A continuous score retains information about the level of reported pain rather than reducing each participant's experience to a simple yes-or-no category. Comparing group means can describe whether the average recorded score was higher or lower between the randomized groups. The standard deviation describes variability among individual scores around each group mean; it does not describe the uncertainty in the mean difference.

The endpoint is relevant to the trial's stated focus on postoperative analgesia, but its interpretation is bounded by the measurement period and the way scores were summarized. It describes average pain during the stated postoperative period, not every aspect of recovery or longer-term pain. The registry record does not report a threshold for a clinically important difference in VRS score, so statistical comparisons alone cannot establish the importance of a difference to patients.

7. Results Posted in the Registry

• Epidural Analgesia With Bupivacaine: mean 4.20 versus 4.30 on control; difference -0.10 (95% CI -0.42 to 0.22), standardized effect d = -0.06; z-test p = 0.536.

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.

Hemodynamic Instability, Defined as Mean Arterial Pressure (MAP) <55 mmHg or Systolic Blood Pressure <80 mmHg.

• 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:
  • Epidural Analgesia With Bupivacaine: mean 57.00 versus 41.00 on control; difference 16.00 (95% CI 5.78 to 26.22), standardized effect d = 0.40; z-test p = 0.002.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Epidural Analgesia With Bupivacaine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes cover several aspects of postoperative recovery, including activity duration, opioid-related side effects, hemodynamic instability, quality of recovery after anesthesia, and hospital stay. The registry lists five secondary outcomes, but it does not report complete results for every one in the record described. The available information is therefore not enough to establish a consistent direction of effect across the secondary outcomes as a group.

Secondary outcomes can add context to the primary pain-score comparison, but they address different questions and may use different measurement scales and analysis methods. They should not be treated as interchangeable with the primary endpoint or as a substitute for its result. A secondary measure could differ between groups even when the average pain scores are close, because the outcomes represent distinct aspects of recovery.

Unadjusted secondary results generally carry less confirmatory weight when many outcomes or analyses are considered. As general statistical context, testing multiple outcomes increases the chance that at least one result appears statistically notable by chance, unless the analysis plan accounts for multiplicity. The registry record does not report whether a multiplicity adjustment or prespecified hierarchy was used. Consequently, secondary findings should be read as supportive or exploratory rather than treated as independent proof of a broad treatment effect.

The primary result and secondary outcomes also differ in how completely they are described in the record. The missing detail limits assessment of consistency, precision, and the relation between outcomes. Results for secondary endpoints not reported in the registry record cannot be inferred from the listed outcome names or from the primary result.

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

• Cumulative Duration of Activity
• Opioid-related Side Effect
• Hemodynamic Instability, Defined as Mean Arterial Pressure (MAP) <55 mmHg or Systolic Blood Pressure <80 mmHg.
• Quality of Recovery After Anesthesia
• Length of Hospital Stay

9. Statistical Interpretation

10. Statistical Methods Explained

Statistical methods describe how the trial turns observations into an estimate and how uncertainty around that estimate is assessed. The registry reports a mixed models analysis for the primary outcome and labels it non-inferiority. It also permits an unadjusted recalculation using the posted means, standard deviations, and group sizes. These approaches should be kept distinct: the recalculation is not a reproduction of the sponsor's model.

What does a mean difference represent?

For a continuous outcome such as VRS pain score, a mean difference expresses the separation between the group averages on the outcome's original scale. Its sign depends on which group is subtracted from which. The posted group means are 4.3 for TAP block with Exparel and 4.2 for epidural analgesia with bupivacaine. The unadjusted recalculation reports a mean difference of -0.1. This small estimate describes the difference in average scores under that calculation; it does not describe the range of individual scores or establish that the groups are equivalent.

As general statistical context, a mean is a summary of the center of a distribution, while a standard deviation describes how dispersed individual observations are around that center. Both groups have a reported standard deviation of 1.8. A standard deviation is not a confidence interval and should not be read as the uncertainty around the estimated difference between group means.

What does the confidence interval add?

As general statistical context, a confidence interval gives a range of estimates compatible with the data and the assumptions of the method. It conveys uncertainty that a point estimate alone does not show. The recalculated interval extends across zero, in keeping with its p-value of 0.536 for an unadjusted comparison. The sponsor's interval is different and is reported as part of a mixed models non-inferiority analysis. Because the discrepancy is flagged, the sponsor's analysis takes precedence when describing the trial's own result.

A confidence interval does not automatically answer whether a difference matters clinically. That requires an interpretation threshold or clinical context. For non-inferiority, the interval must also be considered in relation to a prespecified margin. The margin is not reported in the registry record, so the non-inferiority result cannot be independently evaluated against that criterion from the record alone.

What is a non-inferiority analysis?

As general statistical context, a non-inferiority analysis asks whether the data are sufficiently compatible with an intervention being no worse than a comparator by more than a defined margin. The margin must be chosen before examining the results and is central to the interpretation. A p-value attached to a non-inferiority test has meaning within that framework; it is not a general test that the treatments differ, nor is it evidence of superiority by itself. Here, the record identifies the sponsor analysis as non-inferiority but does not report its margin or the original analysis plan. That missing information limits independent assessment of the claim.

The sponsor's reported estimate is 0.09, with a 95.2% confidence interval from -0.12 to 0.30 and p < 0.001. These values should be read as the sponsor's analysis, not as the recalculated unadjusted comparison. The registry's description does not give sufficient methodological detail to reconstruct the mixed model, such as its covariates or handling of repeated measurements. Those details are not reported in the registry record.

What does the unadjusted recalculation do?

As general statistical context, an unadjusted comparison uses the group summaries without incorporating additional covariates or the structure of a fitted model. It is useful as a transparent check on the direction and scale implied by the posted means, but it may not match an analysis that adjusts for baseline information or other design features. The recalculated p-value of 0.536 belongs to this unadjusted comparison. It should not replace the sponsor's mixed models analysis, especially because the record flags a discrepancy.

The trial's allocation was randomized, which supports comparing outcomes between assigned groups, but it does not make every possible analysis identical. Choice of analysis population, adjustment variables, outcome handling, and model assumptions can all affect estimates and uncertainty. The registry record does not report enough detail to establish the sponsor's choices for each of these elements.

Why can over-dispersion matter?

As general statistical context, over-dispersion occurs when observed variability exceeds what a model assumes. In analyses of counts or binary events, failing to account for over-dispersion can make uncertainty appear too small. The primary endpoint is continuous and is summarized with means and standard deviations, so over-dispersion is not the main issue in interpreting that primary comparison. It can still be relevant in some secondary-outcome models, depending on the outcome and model specification. The registry record does not provide sufficient detail to assess whether over-dispersion was considered in every secondary analysis.

Overall, the methods call for separating the sponsor's formal non-inferiority analysis from the simple recalculation, reading estimates together with their intervals, and recognizing what the registry does not report. A statistical result is conditional on its model and analysis plan; it is not a stand-alone verdict about every aspect of postoperative analgesia.

11. Confidence Intervals and Precision

Precision concerns how much uncertainty surrounds an estimate. For the primary outcome, the recalculated mean difference is -0.1 and the unadjusted p-value is 0.536. Its confidence interval extends from a negative value to a positive value, so the data are compatible with differences in either direction under that calculation. The posted confidence limits for this recalculation have more than three decimal places, so they are not reproduced.

The sponsor's analysis reports a mean difference of 0.09 and a 95.2% confidence interval from -0.12 to 0.30. This is a separate model-based result, not another expression of the recalculated interval. Its limits also lie on both sides of zero. The registry classifies the analysis as non-inferiority, but the non-inferiority margin is not reported, and the interval therefore cannot be assessed against that margin from the registry record.

As general statistical context, narrower intervals indicate greater precision under the assumptions of the analysis, while wider intervals indicate more uncertainty. An interval that includes zero does not establish that the true difference is exactly zero; it indicates that the data do not rule out zero under the stated method. Nor does an interval by itself determine whether any plausible difference is important to patients. The registry record does not report a threshold for a clinically important VRS difference.

The group standard deviations of 1.8 describe variability in individual pain scores, not precision of the between-group estimate. The difference between those concepts matters: people can have varied scores within each group while the group-level estimate has its own uncertainty. Given the disagreement between the sponsor analysis and the recalculation, precision should be discussed alongside the analysis method rather than by quoting one interval in isolation.

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 participants per arm because the primary endpoint is continuous; they are not total event counts. They illustrate the group size that a hypothetical study would require under the stated assumptions, using the observed effect or a smaller proportion of it. The planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is the stated proportion of the observed effect.

The 80% power column means the planning illustration targets an 80% chance of detecting the chosen effect if that effect is the true one and the assumptions hold. The 90% power column uses a higher target chance of detection. These are design targets, not guarantees for an actual trial. The illustration is based on the observed effect, not on a documented original design calculation.

When the target effect is smaller, more participants are needed to distinguish it from random variation with the same significance level and power target. Thus planning for 75% or 50% of the observed effect requires larger group sizes than planning for the full observed effect. The figures are especially sensitive to the observed primary estimate: a small observed difference can lead to very large planning estimates, and those figures should not be mistaken for a clinical recommendation about the size of a future study.

The original trial's sample-size assumptions and justification are not reported in the registry record. The planning figures are not observed power; they are forward-looking illustrations based on specified assumptions and the observed effect. They do not explain why the trial enrolled its reported number of participants or establish that the trial was adequately powered for every endpoint.

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 = -0.100; pooled standard deviation σ = 1.800.
2. n = 2 × (1.96 + 0.842)² × 1.800² / -0.100² = 5,086.1, rounded up to 5,087 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 <- -0.0999999999999996                      # observed difference in means
sigma <- 1.8                     # 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(2996227)
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 = 5,087 (80% power), 6,809 (90% power)
 75% of observed effect: n per arm = 9,042 (80% power), 12,105 (90% power)
 50% of observed effect: n per arm = 20,345 (80% power), 27,236 (90% power)
power.t.test: 5087 
Simulated power at n = 5,087 per arm: 0.795 (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. Analyses Reported by the Sponsor

The sponsor's primary analysis is reported as a mixed models analysis of final values. It gives a mean difference of 0.09, a 95.2% confidence interval from -0.12 to 0.30, and p < 0.001, and the registry labels it as non-inferiority. The registry does not state the non-inferiority margin, so the criterion underlying that label cannot be checked from the record alone.

The unadjusted recalculation from the posted summaries instead gives a mean difference of -0.1 and p = 0.536. The recalculated confidence interval differs from the sponsor's reported interval. These analyses should not be blended into a single estimate: one is the sponsor's model-based non-inferiority analysis, and the other is a simple comparison using summary statistics. The recalculation does not reproduce the sponsor's model or test.

The registry record flags a discrepancy between the sponsor result and the recalculation. In that situation, the sponsor's own analysis takes precedence as the trial's reported analysis. The recalculation remains useful as a transparent check of the posted means, but it does not override the trial analysis. The record does not provide enough methodological detail to identify the reason for the discrepancy, and it would be speculative to attribute it to a particular modeling choice or data-handling decision.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a trial evaluates several outcomes, comparisons, or analyses. As general statistical context, the more statistical tests considered, the greater the opportunity for a low p-value to occur by chance somewhere among them. Researchers may address this with a prespecified hierarchy, an adjustment to significance thresholds, or a clearly stated exploratory approach. The registry record does not report whether such a strategy was planned or applied.

The record lists 10 outcome measures and 7 analyses, and it identifies five secondary outcomes. These counts indicate that the primary pain score is not the only result in the trial record. They do not by themselves reveal which outcomes were prespecified as confirmatory, whether any outcomes were added or omitted, or how the analyses were organized. Those details are not reported in the registry record.

Missing data are also relevant. The primary outcome description says two patients in the epidural group had missing outcomes because surgery was cancelled. The primary group summaries list 255 participants for TAP block with Exparel and 241 for epidural analgesia with bupivacaine, while the overall enrollment is 514. The record does not explain how all enrolled participants map to the reported primary outcome groups, or provide a full account of the analysis population and missing-data handling. No assumptions about imputation, exclusion, or intention-to-treat analysis should be inferred.

Randomized assignment can be preserved in an analysis only if the handling of participants after randomization is clear. The registry does not specify whether the sponsor's model included every randomized participant, how cancelled surgeries were handled, or whether other missing values occurred. These omissions matter because analysis populations and missing-data methods can influence estimates and uncertainty.

The registry also does not report an interim-analysis plan, stopping rules, or the original statistical analysis plan. It is therefore not possible to determine from the record whether interim looks were planned or whether the reported analyses follow a prespecified multiplicity strategy. This does not establish that such procedures were absent; it means they are not reported in the registry record.

16. 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 registry reports zero serious adverse events in the TAP block with Exparel group among 255 participants at risk and zero in the epidural analgesia with bupivacaine group among 243 participants at risk. It also reports zero other adverse events and zero deaths in both groups. These are the counts recorded for the stated safety categories.

Zero recorded events do not establish that no harm occurred or that the approaches have identical safety. They describe what the registry reports within the recorded categories and denominators. The safety group size for epidural analgesia is 243, which differs from the primary outcome group size of 241; the record does not explain that difference.

The registry lists no top serious-event terms. The available safety figures do not provide event-by-event detail, severity gradations beyond the serious category, duration of follow-up, or a comparative safety analysis. The counts should therefore be read narrowly as reported event totals, not as a complete account of all possible harms.

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

The results describe average VRS pain scores during the first 72 postoperative hours in a randomized comparison of TAP block with Exparel and epidural analgesia with bupivacaine. The posted means are 4.3 and 4.2, respectively, and both standard deviations are 1.8. These summaries show similar observed group averages, but they do not on their own establish equivalence, non-inferiority, or superiority.

The sponsor reports a mixed models non-inferiority analysis with an estimate of 0.09, a 95.2% confidence interval from -0.12 to 0.30, and p < 0.001. The registry does not report the non-inferiority margin, which is necessary to assess that framework fully. A separate recalculation from the posted summaries gives an estimate of -0.1 and p = 0.536. The record flags the discrepancy, so the sponsor's own analysis takes precedence as the trial's reported result; the recalculation should not be used to replace it.

The findings do not establish that the two approaches are equivalent for all outcomes or all patients. The primary endpoint is an average pain score over a defined time window. It does not capture every aspect of analgesia, recovery, or safety, and the registry does not state a clinically important difference threshold for VRS. The record also does not report complete results for every secondary outcome, the original sample-size justification, or all analysis details.

The most defensible conclusion is limited to the analyses and outcomes documented in the registry. The sponsor's analysis is labeled non-inferiority, but the missing margin prevents independent evaluation of the criterion. The unadjusted recalculation does not find a statistically significant difference. Neither finding should be translated into medical advice or a broad claim that one analgesia strategy is better or worse.

18. Why This Trial Matters Statistically

This trial raises an important statistical distinction between a conventional comparison of group means and a non-inferiority analysis. Similar observed averages do not automatically establish that two approaches are sufficiently close. A non-inferiority conclusion depends on a prespecified margin, and that margin is not reported in the registry record. Its absence limits how fully readers can evaluate the sponsor's stated analysis.

The record also illustrates why analyses based on summary statistics may not match a sponsor's model-based result. The recalculated estimate and p-value differ from the reported mixed models analysis. A simple unadjusted calculation can be a useful check, but it cannot reproduce model choices or participant handling that are not described. The discrepancy is explicitly flagged, and the sponsor's own analysis takes precedence for reporting the trial's result.

Precision matters as much as the point estimate. The sponsor's confidence interval spans values below and above zero, while the non-inferiority margin needed to interpret it is absent. The recalculated interval also spans both signs. Those features underline the difference between a statistical test, the range of estimates compatible with the data, and a judgment about clinical importance.

Finally, the record connects a primary patient-reported pain measure with a broader set of recovery and safety outcomes. Without complete secondary results, a reported multiplicity strategy, and fuller detail on analysis populations and missing data, the record supports a cautious reading rather than a broad synthesis of benefits and harms. Those reporting gaps are statistically important because they shape what can be concluded from the estimates.

19. 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 non-inferiority margin, the original sample-size justification, or enough detail to reconstruct the sponsor's mixed models analysis. These omissions prevent independent evaluation of the non-inferiority criterion and limit explanation of the difference between the sponsor analysis and the unadjusted recalculation. The reason for that discrepancy is not reported.

Although enrollment is listed as 514, the primary outcome summaries list 255 and 241 participants. The record notes two missing outcomes due to surgery cancellation in the epidural group but does not reconcile the full enrollment with the primary outcome group counts. The safety denominators also differ from the primary-outcome group sizes. The registry does not describe the analysis population, additional missingness, or any imputation or exclusion procedures.

The primary endpoint is limited to average VRS pain during the first 72 postoperative hours. The record does not report a clinically important difference threshold, so the clinical meaning of a small separation between group means cannot be determined from the score summaries alone. Full results for every secondary outcome, a multiplicity strategy, an interim-analysis plan, and the statistical analysis plan are also not reported in the registry record.

The study is listed as having no masking. The record does not describe how this may have affected reporting or assessment of the patient-reported pain outcome. This is a consideration for interpretation, not evidence that the scores were biased. The available information also does not support conclusions about outcomes beyond those reported or about patient groups not described in the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Bilateral Transversus Abdominis Plane Block With Exparel Verus Continuous Epidural Analgesia With Bupivacaine — NCT02996227.
• Registry record last updated 2024-01-31; status last verified 2024-01.
• Results first posted 2024-01-31.
• 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.

23. Record Summary

The registry describes a completed randomized, parallel-group trial comparing bilateral TAP block with Exparel against continuous epidural analgesia with bupivacaine for postoperative pain after major abdominal surgery. Enrollment is listed as 514, with no masking.

The primary outcome is average VRS pain score during the first 72 postoperative hours. The sponsor reports a mixed models non-inferiority analysis, but the margin is not reported. A separate unadjusted recalculation differs; the registry flags the discrepancy, and the sponsor's analysis takes precedence as the trial's reported result.

The record also lists secondary recovery and safety outcomes. It does not report complete information on the original sample-size justification, analysis populations, missing-data handling, multiplicity, or all secondary results. These gaps limit independent evaluation and the scope of conclusions that can be drawn from the registry record.