Acetaminophen Before Vaccines for Infants Study (AVIS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Acetaminophen Before Vaccines for Infants Study (AVIS) (NCT00325819), a randomized phase 3 study. The primary outcome is Fever >=38C Within 32 Hours of Vaccination..

2. Clinical Question

The trial’s stated purpose was to assess whether acetaminophen given for routine infant vaccinations could prevent fever or other symptoms. The primary outcome narrows that broad purpose to a specific event, temperature threshold and observation window. It records whether a participant met the fever definition during the 32 hours following vaccination, rather than describing the duration or severity of fever across a longer period.

The reported primary outcome counts were 25 of 175 in the acetaminophen group and 38 of 174 in the placebo group. The posted comparison is a risk difference, with a negative estimate indicating a lower observed event proportion in the acetaminophen group. Its confidence interval includes zero, so the posted data do not pin down the size or direction of the underlying difference with high precision. This describes the registry results; it is not a recommendation about medication use.

3. Trial Design

The Acetaminophen Before Vaccines for Infants Study (AVIS), NCT00325819, is recorded as a completed phase 3 randomized trial with a parallel-group design. Kaiser Permanente is listed as the sponsor. The registry record gives a start date of 2006-05 and a primary completion date of 2009-09. Total enrollment is 374.

The comparison was acetaminophen versus placebo following routine vaccinations. The arm descriptions state that children were randomized 1:1 to receive up to five doses of acetaminophen, 10-15mg per kg, or placebo. The record identifies masking as triple. Further details about who was masked, the randomization procedure, allocation concealment, or how treatment assignments were implemented are not reported in the registry record.

The endpoint results do not use an identical denominator in the two groups: the primary outcome summary lists 175 participants for acetaminophen and 174 for placebo. The registry record notes missing temperature values for one participant in the acetaminophen group and two in the placebo group. It does not explain how these missing measurements were handled in the analysis, nor does it identify the analysis population or state whether all randomized participants were included in each analysis.

The record lists fever as the condition and identifies one primary outcome and secondary outcomes concerning higher fever, unblinding, medical utilization, fussiness, sleep and time lost from work. The full eligibility criteria, details of vaccination schedules, original sample-size justification, and detailed statistical analysis plan are not reported in the registry record. The planning illustrations associated with the posted outcomes are not evidence of the original design assumptions.

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: No significant events followed participant enrollment prior to group assignment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Temperature values were missing for one subject in the acetaminophen group and two subjects in the placebo 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.

Population: Participants who did not receive acetaminophen or placebo due to postal problems (3), who were not given a first dose of acetaminophen or placebo (13) or who were lost to follow-up due to study diary not being returned (6) were not included in analysis.

6. Primary Endpoint

The registry lists the primary outcome as Fever >=38C Within 32 Hours of Vaccination., measured over Fever within 32 hours following vaccination.

The primary endpoint is the percentage of participants with fever, defined as a rectal temperature at least 38C within 32 hours of vaccination. It is a binary outcome: each participant either met that definition during the stated window or did not. The event counts were 25 of 175 in the acetaminophen group and 38 of 174 in the placebo group.

This type of endpoint is used to make the comparison interpretable as the occurrence of a specific, defined event in each group. The temperature threshold specifies what qualifies as fever, and the 32-hour timeframe limits the observation period. The endpoint therefore addresses early post-vaccination fever, not all symptoms, fever at other times, or longer-term outcomes.

Because the outcome is recorded for each participant as an event or no event, the analysis can compare event proportions or express their contrast as a risk difference or risk ratio. These measures answer related but distinct questions: a risk difference describes the absolute separation between group proportions, while a risk ratio describes their relative scale. The registry’s sponsor-reported analysis uses a risk ratio; the recalculated comparison uses a risk difference.

Missing temperature values matter because the primary endpoint depends on an observed temperature within the specified window. The registry record reports missing values in both groups, but does not report the method used to address them. Thus, interpretation should stay tied to the reported outcome counts and analysis rather than assume how participants with missing measurements were classified.

7. Results Posted in the Registry

• Acetaminophen: 14.3% (25/175) versus 21.8% (38/174) on control; risk difference -7.6 percentage points (95% CI -15.6 to 0.5), risk ratio 0.65 (0.41–1.04); unadjusted two-proportion z-test p = 0.067.

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.

Fever >=39C Within 32 Hours of Vaccination.

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Acetaminophen: 0.0% (0/175) versus 1.7% (3/174) on control; risk difference -1.7 percentage points (95% CI -3.7 to 0.2); unadjusted two-proportion z-test p = 0.081.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Acetaminophen and the control. The interval gives the range of effects that remain compatible with the data.

Study Assignment Unblinded

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Acetaminophen: 2.8% (5/176) versus 9.1% (16/176) on control; risk difference -6.2 percentage points (95% CI -11.2 to -1.3), risk ratio 0.31 (0.12–0.83); unadjusted two-proportion z-test p = 0.013.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Acetaminophen than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Medical Utilization

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Acetaminophen: 2.8% (5/176) versus 6.2% (11/176) on control; risk difference -3.4 percentage points (95% CI -7.7 to 0.9), risk ratio 0.45 (0.16–1.28); unadjusted two-proportion z-test p = 0.125.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Acetaminophen and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes covering fever at a higher temperature threshold, whether study assignment was unblinded, medical utilization, infant fussiness, parent and infant sleep time lost, and parent time lost from work. The available numerical summaries include higher-threshold fever, unblinding and medical utilization. Numerical results for fussiness, sleep and time lost from work are not reported in the registry record.

Across the available summaries, the point estimates generally indicate fewer recorded events in the acetaminophen group, although the size and precision of the comparisons vary. The primary fever result also has a lower observed event proportion in the acetaminophen group, but its confidence interval includes the no-difference value. The secondary outcomes therefore add context about other measured events, but do not resolve uncertainty in the primary comparison.

Study assignment becoming unblinded is a different kind of outcome from fever or medical utilization, and should not be interpreted as a direct measure of fever prevention. Medical utilization is reported within 32 hours of vaccination, while the fever outcomes use the same 32-hour window with different temperature thresholds. These distinctions matter when considering whether estimates address similar questions.

Secondary analyses carry less weight than the primary endpoint for the main trial question. General statistical reasoning: examining multiple outcomes creates more opportunities for apparently notable results to occur by chance, especially if no adjustment or outcome hierarchy is used. The registry record does not report whether multiplicity was addressed, so the secondary estimates should be treated as exploratory context rather than as independent confirmation of the primary finding.

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

• Fever >=39C Within 32 Hours of Vaccination.
• Study Assignment Unblinded
• Medical Utilization
• Infant Fussiness
• Parent Time Lost From Sleep
• Infant Time Lost From Sleep
• Parent Time Lost From Work

9. Statistical Interpretation

10. Statistical Methods Explained

The primary comparison concerns a binary event: fever meeting the defined temperature threshold during the stated observation window. For each arm, the event count and number of participants with reported outcome data form the basis of the comparison. The registry’s sponsor-reported method was unadjusted Poisson regression, reporting a risk ratio. A separate simple recalculation uses the posted summary counts to estimate a risk difference. These are different effect measures, so their numerical values should not be compared as if they were on the same scale.

What does a risk difference express?

A risk difference is the event proportion in one group minus the event proportion in the other group. With acetaminophen as the group of interest and placebo as the comparator, a negative estimate indicates a lower observed event proportion in the acetaminophen group. The recalculated estimate is -0.075. Its confidence interval ranges from -0.156 to 0.005. Since zero is included, the interval is compatible with no absolute difference as well as with differences in either direction.

What does a risk ratio express?

A risk ratio divides one group’s event proportion by the other group’s event proportion. A value of 1 corresponds to equal proportions; values below 1 indicate a lower observed proportion in the numerator group, and values above 1 indicate a higher one. The sponsor-reported risk ratio is 0.66, with a 95% confidence interval from 0.41 to 1.01. That interval includes 1. The registry identifies the model as unadjusted Poisson regression. The record does not report covariates used for adjustment; the method is explicitly described as unadjusted.

How should the p-values be read?

The sponsor-reported p-value is 0.053, while the simple recalculation reports 0.067. In general, a p-value evaluates how unusual data at least as incompatible with a null model would be if that model and its assumptions held. It does not state the probability that a treatment effect exists, and it does not quantify the size or practical importance of an effect. General statistical convention sometimes compares p-values with a threshold, but the registry record does not report a decision threshold for the primary result. The estimates and confidence intervals provide more information about the range of plausible contrasts than a p-value alone.

Why do the methods yield different numbers?

The sponsor reports a model-based risk ratio, whereas the recalculation is a simple unadjusted risk difference from the displayed summary counts. Different effect measures have different scales and reference values. The recalculated p-value is also based on a simple unadjusted calculation, not the sponsor’s Poisson regression model. It is therefore expected that the point estimates and p-values need not be identical. The record does not report enough detail about the sponsor’s model implementation to reproduce it fully.

The registry record states that temperature values were missing for one participant in the acetaminophen group and two in the placebo group. General statistical practice recognizes that missing outcome values can affect denominators and estimates, depending on the amount and pattern of missingness and on the analysis method. The record does not state whether participants with missing temperatures were excluded, imputed, or handled in another way. No particular missing-data assumption should be inferred.

Over-dispersion is a general concern when a count model assumes more variability structure than the data support; it can affect uncertainty estimates in some model settings. The primary endpoint is reported as a binary fever outcome, and the record identifies unadjusted Poisson regression for the sponsor’s risk-ratio analysis. It does not report a model diagnostic or an over-dispersion assessment, so no conclusion about that issue can be drawn for this analysis.

Finally, the registry does not report the full analysis plan, the original sample-size justification, the specified analysis population, or whether an interim analysis occurred. Those details can influence how trial estimates and uncertainty are interpreted. Their absence means the posted analysis should be described as reported, without filling gaps through assumptions about the protocol.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data estimate the underlying group contrast. A confidence interval gives a range of values compatible with the data under the method’s assumptions. It is not a guarantee that the true effect falls inside the particular interval, nor does it show the probability that any one effect value is true.

For the recalculated risk difference, the estimate is -0.075 and the 95% confidence interval is -0.156 to 0.005. The interval includes zero, the reference value for no absolute difference. It allows for a lower event proportion in the acetaminophen group, but also extends slightly past zero. Thus the estimate points in one direction, while the interval does not exclude no difference.

The registry-reported risk ratio is 0.66 with a 95% confidence interval from 0.41 to 1.01. The reference value for no relative difference is 1, and this interval reaches slightly above it. The estimate and interval are consistent with a lower observed event proportion in the acetaminophen group, but the uncertainty includes equal proportions. The two intervals are on different scales and should not be compared by their numerical widths alone.

The event counts are modest relative to the total enrollment, and the endpoint has missing temperature values in both groups. General statistical reasoning indicates that estimates based on limited event information can be imprecise, but the registry does not report a formal precision target or a design justification. The interval is the direct evidence about uncertainty in this result; it should be considered alongside the point estimate and the outcome definition.

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 illustrations show the number of participants per arm for the binary outcomes. These are not total event counts. The displayed planning scenarios use the observed effect as a starting point and consider detecting 100%, 75%, or 50% of that effect. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The original trial’s own sample-size assumptions and justification are not reported in the registry record.

The 80% power column means the illustrated number of participants per arm under which the calculation targets an 80% chance of detecting the stated effect if that effect and the planning assumptions hold. The 90% power column describes the corresponding target at 90%. These are design-planning quantities, not probabilities that the observed trial result is correct, and they do not describe the power actually achieved in this completed study.

Smaller effects are harder to distinguish from random variation, so planning to detect a smaller fraction of the observed effect generally requires more participants. This pattern is reflected in the increasing participant requirements as the planning effect moves from 100% to 75% to 50% of the observed effect. The numbers are illustrations based on the observed estimates, not evidence that the original investigators used those assumptions or planned the study around the observed result.

The sample-size figures are not observed power. Observed power is not a useful substitute for reading the effect estimate and its confidence interval after a trial is complete. The interval directly conveys the range of contrasts compatible with the posted data under the stated analysis method.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.218; treatment proportion p₁ = 0.143; average p̄ = 0.181.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5441 = 1.0663.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5414 = 0.4557.
4. n = (1.0663 + 0.4557)² / (-0.0755)² = 406.0, rounded up to 407 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 <- 0.218390804597701                          # control proportion
p1 <- 0.142857142857143                          # 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(325819)
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 = 407 (80% power), 544 (90% power)
 75% of observed effect: n per arm = 752 (80% power), 1,006 (90% power)
 50% of observed effect: n per arm = 1,757 (80% power), 2,351 (90% power)
power.prop.test: 406 
Simulated power at n = 407 per arm: 0.803 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry-reported primary analysis is the sponsor’s own analysis: unadjusted Poisson regression with a risk ratio of 0.66, a 95% confidence interval from 0.41 to 1.01, and p = 0.053. The simple recalculation from the posted outcome counts gives a risk difference of -0.075, a 95% confidence interval from -0.156 to 0.005, and p = 0.067.

The two analyses point toward a lower observed fever proportion in the acetaminophen group, but they use different effect measures and calculation methods. The risk ratio compares proportions multiplicatively, while the risk difference expresses their absolute separation. Their estimates therefore are not numerically interchangeable. The recalculated interval includes zero; the sponsor-reported interval includes 1, the respective no-difference values.

The registry marks no discrepancy between the reported and recalculated analyses. The sponsor’s result is the trial’s reported analysis, and the recalculation is a simple unadjusted check using posted summary information rather than a reproduction of the regression model. The registry does not include enough model detail to independently reconstruct every aspect of that analysis. Interpretation should retain the sponsor’s reported method and its uncertainty rather than treating the recalculation as a replacement.

15. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one primary outcome and lists seven secondary outcomes. It does not report whether the analysis plan specified a hierarchy among outcomes, adjusted for multiple comparisons, or designated which secondary analyses were confirmatory. When multiple outcomes are examined, general statistical reasoning says that unadjusted results can be more vulnerable to chance findings across the set. Without a reported multiplicity strategy, the secondary p-values should not be treated as if each were the only planned comparison.

Missing temperature values are specifically noted for one participant in the acetaminophen group and two in the placebo group. The record does not report how these missing measurements were handled, whether any sensitivity analysis was performed, or whether missingness was related to participant characteristics or outcomes. Consequently, it is not possible to assess from the registry record how alternative missing-data approaches might affect the estimate.

The participant counts listed for the primary endpoint are 175 for acetaminophen and 174 for placebo, while total enrollment is 374. The registry does not state whether the endpoint counts represent an intention-to-treat analysis, a per-protocol analysis, or another analysis population. It also does not report whether all randomized participants were retained in each secondary analysis or how exclusions, if any, were determined.

The original statistical analysis plan, sample-size justification, interim-analysis procedures and any stopping rules are not reported in the registry record. These omissions do not establish that such procedures were absent; they mean the posted record does not allow them to be described or assessed. Interpretation should therefore stay with the endpoints, estimates, methods and limitations explicitly recorded.

16. 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 0% reporting threshold.

The serious adverse event summary records zero serious events among 176 participants at risk in the acetaminophen group and zero among 176 at risk in the placebo group. It also records zero other adverse events among 176 at risk in each group. Death counts are not reported in the registry record.

These figures describe what was entered in the registry’s adverse-event summary. A zero count means no events of that category were recorded in the listed groups; it does not establish that an event is impossible, or that the study could rule out uncommon harms. The registry does not provide serious-event terms, with the serious-event term list empty, and does not give further detail about event ascertainment or follow-up for safety.

Safety counts should be read separately from the primary fever outcome. The serious adverse event summary does not answer the primary endpoint question, and it should not be interpreted as a comprehensive assessment of all possible effects. It is limited to the event categories and at-risk counts recorded in the registry.

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

The central observation is that fewer participants in the acetaminophen group met the registry’s fever definition during the stated period than in the placebo group. The risk-difference estimate is -0.075, and the sponsor-reported risk ratio is 0.66. Both express a point estimate in the direction of a lower observed fever proportion with acetaminophen. However, the confidence intervals include their respective no-difference values, so the posted data do not precisely distinguish a group difference from no difference.

This result concerns rectal temperature at least 38C within 32 hours following vaccination. It does not directly answer whether other symptoms changed, whether fever occurred after that interval, or whether effects were sustained. The registry lists several secondary questions, but some numerical outcomes are not reported in the registry record. The trial’s measured outcome should not be broadened into a claim about every symptom or every aspect of post-vaccination experience.

Statistical uncertainty and practical importance are different questions. A confidence interval describes uncertainty in the estimated group contrast under its assumptions; it does not decide whether a difference matters to families or clinicians. The registry record does not report a threshold for a clinically important difference, nor details of the protocol that would establish one. No treatment recommendation follows from the numbers alone.

The results also depend on the way the endpoint and analysis were defined. Temperature values were missing for participants in both groups, and the registry does not describe their handling. It does not report the original sample-size rationale, analysis population, multiplicity adjustment or full statistical plan. Those limitations constrain what can be concluded beyond describing the observed results and their reported precision.

18. Why This Trial Matters Statistically

This trial illustrates why a point estimate should be read together with its uncertainty. The observed event proportions favor one direction, yet the risk-difference and risk-ratio confidence intervals include their respective no-difference values. Focusing only on which group’s observed proportion is lower would omit the central statistical issue: the range of contrasts compatible with these data is broad enough to include no difference.

It also demonstrates that the same trial comparison can be expressed using different measures. The sponsor-reported risk ratio and the simple recalculated risk difference answer related but distinct questions. Their reference values differ, and their numerical scales are not interchangeable. Clear interpretation requires naming the measure, its comparator and the no-difference value, rather than treating every estimate as a generic effect.

The record is also a useful reminder that missing outcome measurements and analysis populations are part of statistical interpretation, not administrative details. The registry notes missing temperatures, but does not explain the analysis handling. It gives group counts for the endpoint, but not the population definition. Those gaps limit independent assessment of the reported comparison.

Finally, secondary outcomes and planning calculations require appropriate context. Multiple secondary comparisons can generate chance findings, and a planning illustration based on an observed estimate is not evidence of actual power or the original trial rationale. Keeping primary and secondary questions distinct, and distinguishing planning quantities from trial results, helps prevent stronger conclusions than the record supports.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record reports missing temperature values in both groups but does not describe how missing outcomes were handled. This matters because the primary endpoint depends on a measured rectal temperature within a specified window. The record also does not identify the primary analysis population or state whether all randomized participants were included in the analysis.

The full protocol and statistical analysis plan are not reported in the registry record. In particular, the original sample-size justification, any interim analyses, analysis decision thresholds, multiplicity procedures, and detailed model specifications are not reported. The posted planning illustrations are based on the observed effect and cannot substitute for the trial’s original design rationale.

The primary finding is imprecise: the risk-difference confidence interval includes zero, and the sponsor-reported risk-ratio confidence interval includes 1. The sponsor’s analysis and the simple recalculation also use different effect measures and methods. The registry does not provide enough model detail to independently reproduce the sponsor’s regression analysis.

Some secondary outcomes are listed without numerical results in the registry record, limiting assessment of the full range of symptoms and related measures named as study outcomes. The safety summary records no serious adverse events in either group, but the record gives limited detail about safety ascertainment and does not report death counts. These are limits of the registry information; they should not be taken as evidence that the relevant protocol procedures or additional analyses did not exist.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Acetaminophen Before Vaccines for Infants Study (AVIS) — NCT00325819.
• Registry record last updated 2017-10-13; status last verified 2017-10.
• Results first posted 2014-04-07.
• 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

NCT00325819, the Acetaminophen Before Vaccines for Infants Study (AVIS), is recorded as a completed phase 3 randomized, triple-masked, parallel-group trial sponsored by Kaiser Permanente. Enrollment was 374. The trial compared acetaminophen with placebo following routine infant vaccinations.

The primary outcome was fever, defined as rectal temperature at least 38C within 32 hours of vaccination. The registry-reported analysis gave a risk ratio of 0.66, with a 95% confidence interval from 0.41 to 1.01 and p = 0.053. A simple unadjusted recalculation gave a risk difference of -0.075, with a 95% confidence interval from -0.156 to 0.005 and p = 0.067. Both intervals include their respective no-difference values.

The record notes missing temperature values in both groups, but does not report their handling or the full analysis plan. The reported results describe the observed comparison and its uncertainty; they do not alone establish whether the observed contrast is clinically important.