A Study of the Safety and Immune Response to RotaTeq™ Vaccine in the Elderly (V260-027): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Safety and Immune Response to RotaTeq™ Vaccine in the Elderly (V260-027) (NCT00836498), a randomized phase 1 study. The primary outcome is Part I: Number of Participants With Nonserious and Serious Adverse Experiences (AEs).

2. Clinical Question

This is a safety and immunogenicity study in an elderly population, not a trial designed in the posted record to establish clinical prevention of rotavirus illness. The primary outcome counts participants with at least one adverse experience; it does not count the total number of experiences. A participant with multiple reported experiences still contributes as a participant with an event to that summary. The trial’s stated age range, groups, and observation window define the context for interpreting the counts, while details such as the full statistical protocol are not reported in the registry record.

3. Trial Design

The registry record describes a Phase I, randomized, double-blind, parallel-group study of RotaTeq™ and placebo. The brief summary lays out a two-part plan. Part I was to include approximately 60 participants in the United States, randomly assigned to receive 3 doses of RotaTeq™ or placebo. Part II was planned as an international component with approximately 200 participants across three treatment groups. It was to start only after Part I data analysis had been reviewed and approved by the FDA/CBER, the Safety Evaluation Committee, and other regulatory agencies.

The sponsor’s business decision meant that the study did not proceed with Part II. Consequently, the posted report contains Part I results only. The registry record lists 66 participants enrolled overall and the primary-outcome groups contain 44 RotaTeq™ participants and 22 placebo participants. The planned Part I enrollment and the posted analyzed group sizes are not identical descriptions: the former is an approximate plan, while the latter are the counts attached to the posted primary outcome.

The record’s status is terminated. It lists a start date of 2009-01 and primary completion in 2010-01. The proposed study duration for the entire study was approximately 4 years, but that plan included Part II, which did not proceed. The record does not state that the original full study duration was achieved.

The intervention entries also include Part II schedules, including a group assigned 1 dose of RotaTeq™ and 2 doses of placebo. Those planned groups should not be mistaken for participants in the posted Part I comparison. Further details of sequence generation, allocation concealment, masking procedures, site conduct, protocol deviations, and the trial’s own sample-size rationale are not reported in the registry record. The randomized and double-blind labels describe the design, but do not supply those operational details.

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: Part II was not conducted; no participants were recruited.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized participants who received at least one dose of RotaTeq™ or placebo are included in the summaries. Number of participants with one or more adverse experience.

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 Part I: Number of Participants With Nonserious and Serious Adverse Experiences (AEs), measured over Up to 42 days following any dose of RotaTeq™ or placebo.

The primary endpoint is the number of participants with one or more nonserious or serious adverse experiences. The observation timeframe is up to 42 days following any dose of RotaTeq™ or placebo. The population description specifies randomized participants who received at least one dose. This is a participant-level event summary: it records whether a participant had an adverse experience, not how many separate experiences that participant had.

Safety outcomes are included in early-phase studies to describe events observed during and after exposure and to support monitoring of participants. The registry description says participants were contacted by telephone or in-center visit on Days 7, 14, 28, and 42 after each dose. Participants received a Vaccination Report Card at each vaccination visit, with instructions to record adverse experiences and potential acute gastroenteritis episodes within 42 days after any dose. These procedures describe how events were solicited and recorded; they do not establish that every reported event was caused by the assigned intervention.

The endpoint combines serious and nonserious experiences into a count of participants with at least one event. Separate serious and other adverse-event summaries give additional context, but a count alone does not describe event severity, duration, recurrence, or causal attribution. The registry record does not report an endpoint definition that assigns causality to the intervention. The endpoint is therefore best read as a safety-event summary over the stated follow-up period, not as a direct measure of vaccine benefit or proof of cause.

7. Results Posted in the Registry

• RotaTeq™: 59.1% (26/44) versus 40.9% (9/22) on control; risk difference 18.2 percentage points (95% CI -7.0 to 43.3), risk ratio 1.44 (0.83–2.53); unadjusted two-proportion z-test p = 0.163.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level event indicator: a participant either had one or more adverse experiences in the stated period or did not. The reported numbers are counts of participants, while the arm sizes provide the denominators for the comparison. This distinction matters because event counts and participant counts can differ when an individual experiences more than one event. The primary measure concerns participants with an event, not the total number of events.

What does the risk difference describe?

The risk difference compares the proportion of participants with an event in one group with the corresponding proportion in the comparator group. The posted group proportions are 0.591 for RotaTeq™ and 0.409 for placebo. The risk difference is 0.182. A positive value means the observed event proportion was higher in the RotaTeq™ group for this comparison; a value of zero would indicate equal observed proportions. The interval from -0.070 to 0.433 represents uncertainty around the estimated difference. Because it includes zero, the data do not isolate a nonzero difference with precision.

How do relative measures differ?

A risk ratio compares the event proportions as a ratio, whereas an odds ratio compares the odds of an event. The posted risk ratio is 1.444, with an interval from 0.826 to 2.527; the odds ratio is 2.086, with an interval from 0.737 to 5.908. A ratio of 1 corresponds to equal values between groups. Both intervals include 1, and both are wide. Relative measures can look numerically larger than an absolute difference because they use different scales. Neither scale removes the uncertainty created by the limited number of participants.

What does the p-value say?

The unadjusted p-value is 0.163. In general, a p-value measures how compatible the observed data are with a specified null model, under the assumptions of the statistical test. It is not a measure of effect size, a probability that the null model is true, or a measure of clinical importance. Because the registry record does not report the original inferential plan, the posted unadjusted p-value should not be assumed to account for every analysis decision or for multiple outcome testing.

For a binary outcome, precision depends on both the event proportions and the number of participants contributing to them. A larger sample can generally provide more information, while a small group can leave a broad range of plausible values. Here, the primary comparison includes 44 participants assigned to RotaTeq™ and 22 assigned to placebo. The unequal group sizes and limited overall numbers are relevant context for the width of the reported intervals; they do not change the definition of the effect measures.

What does randomization contribute?

Random assignment is intended to make the groups comparable in expectation, reducing systematic differences in measured and unmeasured characteristics. It does not guarantee identical groups in a study of this size. Double masking is intended to reduce influences of treatment knowledge on participant reports and outcome assessment, though the registry record does not describe the masking procedures in detail. These design features support a fairer comparison, but do not eliminate uncertainty or establish that an observed event was caused by an intervention.

The primary outcome combines serious and nonserious adverse experiences. That aggregate can be useful as a broad safety summary, but it does not give equal clinical meaning to every event. The separate serious-event summaries help distinguish serious events from other events, while the listed terms provide further event descriptions. Counts in those summaries remain descriptive and should be interpreted with their denominators and the limited follow-up context in mind.

The posted comparison is unadjusted. The registry record does not report details of the test used for the p-value, covariate adjustment, stratification, missing-data imputation, sensitivity analyses, or multiplicity control. It also does not report interim analyses or the study’s original sample-size justification. These absences limit how much can be inferred about the intended confirmatory role of the comparison. They do not invalidate the descriptive counts, but they constrain interpretation of inferential claims.

Finally, the trial’s two-part plan and the posted Part I results must be kept distinct. Part II was conditional on review of Part I and did not proceed following a sponsor business decision. Analyses and groups planned for Part II cannot be treated as observed data. The statistical interpretation therefore applies only to the posted Part I safety comparison and other results actually recorded, not to the full set of outcomes contemplated in the initial study description.

10. Confidence Intervals and Precision

The risk-difference estimate is 0.182, and its reported interval runs from -0.070 to 0.433. This span is substantial relative to the point estimate and includes zero. In practical statistical terms, the posted data allow a range of plausible between-group differences, including no difference and differences in either direction. The point estimate alone should not be treated as a precise description of the effect.

The relative estimates are also imprecise. The risk ratio is 1.444, with a reported interval from 0.826 to 2.527. The odds ratio is 2.086, with a reported interval from 0.737 to 5.908. Each interval includes the value corresponding to no between-group association on its respective scale. Their broad ranges are consistent with considerable uncertainty in this small comparison.

A confidence interval is a statistical range constructed by a method that, over repeated samples under its assumptions, is intended to capture the target parameter at its stated coverage level. The registry record does not state the coverage level or method for these intervals, so those details are not reported in the registry record. Regardless of the precise method, the displayed endpoints show that the estimate is not tightly determined by the observed data.

Precision is distinct from whether a result crosses a conventional decision threshold. A wide interval can reflect limited information even when a point estimate appears notable. The arm sizes—44 for RotaTeq™ and 22 for placebo—are important context for the uncertainty. These intervals describe statistical uncertainty in the posted comparison; they do not account for every possible concern, such as unreported missing-data procedures or unreported multiplicity handling.

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 display is a planning illustration based on the observed effect, not the trial’s original design calculation. Its entries are participants per arm, rather than total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; each planning scenario uses the stated fraction of the observed effect to detect. The trial’s own original sample-size assumptions are not reported in the registry record.

For planning at 100% of the observed effect, the display gives 118 participants per arm for 80% power and 157 participants per arm for 90% power. For planning at 75% of the observed effect, it gives 210 participants per arm for 80% power and 280 participants per arm for 90% power. For planning at 50% of the observed effect, it gives 470 participants per arm for 80% power and 629 participants per arm for 90% power.

In general, the 80% power column represents the planned chance of detecting the specified effect under the stated model and assumptions if that effect is real; the 90% column uses a higher target chance under those same assumptions. Smaller effects are harder to distinguish from random variation, so planning to detect a smaller fraction of the observed effect requires more participants per arm. The display is not observed power: it does not measure the probability that this completed Part I study detected an effect, nor does it change the interpretation of the observed confidence interval.

The curve should be read in the same planning context, as a depiction of how the required sample size changes with the effect used for planning under the stated assumptions. It is not evidence that the trial enrolled those numbers or that a particular effect was achieved. Since Part II did not proceed, these illustrative requirements should not be confused with the actual groups in the posted Part I outcome.

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 = 0.409; treatment proportion p₁ = 0.591; average p̄ = 0.500.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7071 = 1.3859.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6953 = 0.5852.
4. n = (1.3859 + 0.5852)² / (0.1818)² = 117.5, rounded up to 118 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 <- 0.409090909090909                          # control proportion
p1 <- 0.590909090909091                          # 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(836498)
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 = 118 (80% power), 157 (90% power)
 75% of observed effect: n per arm = 210 (80% power), 280 (90% power)
 50% of observed effect: n per arm = 470 (80% power), 629 (90% power)
power.prop.test: 117.5 
Simulated power at n = 118 per arm: 0.797 (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 lists several secondary immune-response outcomes, including geometric mean titers for rotavirus serotypes G1, G2, G3, G4, and P1A[8], as well as a Part II outcome concerning participants with a 3-fold rise from baseline. These are listed as planned or registered outcomes, but their analyses are not reported in the registry record. The planned Part II outcomes should also be distinguished from Part I results because Part II did not proceed.

Multiplicity arises when several outcomes or comparisons are tested: without an appropriate strategy, the chance of at least one chance finding can increase across a family of tests. The registry record does not report a multiplicity adjustment, a hierarchy of endpoints, or a strategy distinguishing confirmatory from exploratory analyses. The unadjusted p-value should therefore not be read as though the record establishes control of error across all listed outcomes.

The primary population is described as all randomized participants who received at least one dose. The record also says all randomized participants were contacted after each dose. It does not report how missing outcome information was handled, whether any participants lacked follow-up, or whether analyses used imputation or other missing-data methods. Details of a full intention-to-treat population, per-protocol population, exclusions after randomization, and sensitivity analyses are not reported in the registry record.

These reporting gaps do not alter the posted group counts, but they limit assessment of how the analysis addressed incomplete data and the many listed outcomes. The registry record also does not report interim analyses or a prespecified statistical analysis plan. Interpretations of inferential results should remain tied to what is explicitly recorded: the primary event counts, the unadjusted comparison, and the stated analysis population.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: coronary artery disease (2.3%), cerebrovascular accident (2.3%).

For serious adverse experiences, the registry record reports 2 of 44 participants in the RotaTeq™ group and 0 of 22 in the placebo group. For other adverse experiences, it reports 18 of 44 and 4 of 22, respectively. These are participant counts in the safety summaries; they should not be interpreted as proof that the intervention caused an event. The number of deaths is not reported in the registry record.

The serious-event terms listed are coronary artery disease at 2.3% and cerebrovascular accident at 2.3%. The registry record does not provide enough detail to assign these terms to a particular participant group or to establish causality. The percentages should be read as registry-reported values, not recomputed from the group counts.

Serious events are uncommon in a small study, so a small count can be difficult to compare reliably between groups. The summaries do not describe event timing, participant-level overlap among terms, or a causal assessment. They are safety observations during the recorded study period, not a stand-alone estimate of risk beyond the trial’s follow-up.

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

The posted Part I primary result shows that 26 of 44 RotaTeq™ participants and 9 of 22 placebo participants had one or more adverse experiences in the stated period. The risk-difference point estimate is 0.182, and the reported interval from -0.070 to 0.433 is broad and includes zero. The data therefore describe a higher observed event proportion in the RotaTeq™ group, while leaving substantial uncertainty about the size and direction of the underlying difference.

This finding does not establish that RotaTeq™ caused the recorded events. The endpoint is based on reported adverse experiences, and the registry record does not provide a causal attribution analysis. Nor does the primary safety comparison answer whether the vaccine produced an immune response: immune-response outcomes are listed, but their analyses are not reported in the registry record.

The study should not be interpreted as having completed the full two-part plan. Part II did not proceed following a sponsor business decision, so the posted results are limited to Part I. The planned international groups and their treatment schedules do not contribute evidence to the reported primary comparison.

The findings also do not establish what might happen outside the recorded follow-up or in populations not described by the Part I age range and setting. The small group sizes and wide intervals constrain precision. Statistical uncertainty is not the same as evidence that there is no difference; equally, a point estimate in one direction is not proof of a real or clinically important difference.

Accordingly, the record supports a cautious description of observed safety-event counts in this randomized, double-blind Part I comparison. It does not support a broad conclusion about effectiveness, causation, or outcomes for the uncompleted Part II. The registry’s missing information on analysis planning and missing data further limits claims beyond the posted summaries.

16. Why This Trial Matters Statistically

This study illustrates why early-phase safety results need to be read alongside the design, event definition, and uncertainty around estimates. A participant-level count of adverse experiences gives a direct summary of how many people had at least one event, but it does not show the total number of events, their duration, or whether they were attributed to treatment. The distinction is important when interpreting a broad endpoint that combines serious and nonserious experiences.

The comparison also shows why point estimates should not be read alone. The observed risk difference is 0.182, but its interval extends from -0.070 to 0.433. A single estimate can suggest a direction; the interval conveys that the underlying difference remains uncertain. The relative estimates are similarly imprecise, reinforcing the need to consider scale and uncertainty together.

Trial status and completion matter statistically. The initial plan included a Part II, but the registry record says it did not proceed. Conclusions must therefore be limited to the available Part I results, rather than treating planned groups or outcomes as observed evidence. This distinction is especially relevant when a registry record contains a broad original plan alongside a narrower posted report.

Finally, the record lists immune-response outcomes without analyses and does not report a full statistical plan, missing-data methods, or multiplicity strategy. These limits illustrate why registry interpretation should separate recorded results from planned outcomes and distinguish descriptive evidence from a complete inferential assessment. The result is informative as a small randomized safety comparison, but its scope and precision are limited.

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.

Several features limit interpretation of this trial’s results. Part II did not proceed, so the posted evidence covers only Part I rather than the full international plan described in the brief summary. The status is terminated, and the registry record does not explain beyond the business decision that Part II was not undertaken. The planned total study duration of approximately 4 years should not be mistaken for observed follow-up of that length.

The primary safety groups are modest in size and unequal: 44 participants received RotaTeq™ and 22 received placebo in the posted outcome. The risk-difference and relative-effect intervals are broad, reflecting limited precision. Counts of serious events are particularly sparse. The registry record does not report deaths, event-level timing, participant overlap among serious-event terms, or causal attribution.

The record describes contact and event-reporting procedures, but does not report the completeness of follow-up, missing-data handling, protocol deviations, adherence, or analysis populations beyond the stated primary population. It does not provide the trial’s original sample-size justification, a detailed statistical analysis plan, interim-analysis details, or a multiplicity strategy. Such information would be needed to assess whether the posted inferential comparisons followed prespecified procedures.

Immune-response measures are listed, but their analyses are not reported in the registry record. The result therefore cannot answer the study’s immunogenicity question from the posted primary endpoint alone. These limitations do not negate the descriptive safety counts; they define the boundaries of what those counts and estimates can support.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Study of the Safety and Immune Response to RotaTeq™ Vaccine in the Elderly (V260-027) — NCT00836498.
• Registry record last updated 2015-05-01; status last verified 2015-04.
• Results first posted 2011-02-04.
• 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 describes NCT00836498, a randomized, double-blind, parallel-group Phase I study of RotaTeq™ and placebo in elderly participants. Its stated primary safety outcome is the number of participants with one or more serious or nonserious adverse experiences up to 42 days following any dose.

The posted primary results are from Part I: 26 of 44 participants in the RotaTeq™ group and 9 of 22 in the placebo group experienced at least one adverse experience. The risk difference is 0.182, with a reported interval from -0.070 to 0.433; the unadjusted p-value is 0.163. Part II did not proceed following a sponsor business decision, and immune-response analyses are not reported in the registry record.