The Effect of Aromatherapy on Neonatal Abstinence Syndrome and Salivary Cortisol Levels: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effect of Aromatherapy on Neonatal Abstinence Syndrome and Salivary Cortisol Levels (NCT03097484), a randomized phase 3 study. The primary outcome is Length of Hospitalization.

2. Clinical Question

The trial asks whether adding lavender and chamomile aromatherapy to standard therapy is associated with different lengths of hospitalization and medication therapy for infants with neonatal abstinence syndrome. The registry describes the aromatherapy as essential oils and compares the combined care with standard care alone.

The question is specific to this care setting and these outcome measures. It is not a direct test of aromatherapy in isolation, because the comparison concerns aromatherapy added to a package of standard care. The record does not report additional details about the infants’ clinical profiles or the delivery and duration of the aromatherapy.

3. Trial Design

The registry describes a randomized, parallel-group, Phase 3 trial that is completed. Enrollment was 38. The record lists 19 participants in the standard-therapy-alone arm and 19 in the standard-therapy-plus-aromatherapy arm. A parallel design assigns participants to one of the study arms, so the reported group outcomes compare separate groups rather than repeated measurements of the same infants.

The trial was unmasked: the registry lists no masking. In general, masking can reduce the influence of knowledge about assigned care on some aspects of study conduct or assessment. With no masking reported, the record does not indicate that participants or relevant study personnel were kept unaware of group assignment. The registry does not describe any steps taken to limit possible effects of unmasked assignment.

The aromatherapy intervention consisted of lavender and chamomile essential oils, in addition to standard care. Standard care is described as morphine replacement therapy, infant massage, physical therapy, occupational therapy, and music therapy. The comparator received those standard-care components without aromatherapy. The record does not report further information about how often aromatherapy was administered, its duration, or how adherence was assessed.

The listed study dates are a start date of 2015-07-25 and a primary completion date of 2017-04-30. The overall status is completed. The registry reports the primary endpoint as length of hospitalization, in days, over a timeframe of up to 4 months. Length of medication therapy, also measured in days over a timeframe of up to 4 months, is listed as a secondary outcome.

The registry does not report the original sample-size justification, the trial’s detailed statistical analysis plan, or whether interim analyses were planned or conducted. The participant counts and reported outcome statistics describe the posted results; they do not establish what assumptions guided the original trial design.

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

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 Length of Hospitalization, measured over Up to 4 months.

The primary endpoint is length of hospitalization, measured in days. It represents how long an infant remains hospitalized. The registry specifies a mean as the summary measure and a standard deviation as the measure of spread, with an outcome timeframe of up to 4 months.

Length of stay is a continuous outcome: it can take a range of numerical values rather than placing each participant into a simple category. Comparing group means gives a concise description of average hospitalization duration in the two randomized arms. The standard deviations add context about how much individual lengths of stay varied within each arm. In this trial, the standard-therapy-alone group had a mean of 17.8 days and a standard deviation of 10.1; the standard-therapy-plus-aromatherapy group had a mean of 11.4 days and a standard deviation of 6.6.

In general, a group mean is useful for describing the average outcome, but it does not show every participant’s experience or the shape of the outcome distribution. A standard deviation describes variation around the group mean, not the precision of the estimated mean difference. The mean difference and its confidence interval address the between-group comparison and its uncertainty.

The primary outcome is the registry’s designated main measure for this trial. It should therefore be distinguished from length of medication therapy, which is posted as a secondary outcome. The registry does not report additional detail about the primary outcome’s operational definition, such as how discharge timing was handled or how missing outcome values were treated.

7. Results Posted in the Registry

• Standard Therapy Plus Aromatherapy: mean 11.40 versus 17.80 on control; difference -6.40 (95% CI -11.83 to -0.97), standardized effect d = -0.75; z-test p = 0.021.

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.

Length of Medication Therapy

• 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:
  • Standard Therapy Plus Aromatherapy: mean 7.40 versus 12.70 on control; difference -5.30 (95% CI -10.61 to 0.01), standardized effect d = -0.64; z-test p = 0.050.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Standard Therapy Plus Aromatherapy and the control. The interval gives the range of effects that remain compatible with the data.

Length of medication therapy is the one secondary outcome posted in the registry. Across the primary and secondary outcomes, the observed group means are lower in the standard-therapy-plus-aromatherapy arm than in the standard-therapy-alone arm. This directional consistency gives the secondary outcome context alongside the primary result, but it does not make the two outcomes interchangeable: hospitalization duration and medication duration measure different aspects of care.

The secondary comparison is less decisive on its own because its recalculated interval reaches zero. Its reported p-value is 0.05, and the registry lists a two-sided t-test. The interval and p-value describe uncertainty under the methods used; neither establishes that a difference is present or absent. The secondary result should be read as a pattern in the posted data rather than a standalone confirmation of the primary outcome.

In general, when a study assesses more than one outcome, the chance of obtaining at least one apparently notable result can increase if each test is interpreted separately without adjustment. A multiplicity plan specifies how that issue is handled. No adjustment for multiple testing is reported in the registry record. This matters particularly for secondary outcomes, which commonly provide additional context but do not carry the same evidential role as the designated primary outcome.

The registry lists one secondary endpoint, length of medication therapy, and does not report further secondary analyses or a hierarchy among outcomes. It also does not report whether the secondary outcome was prespecified in a detailed analysis plan or how missing values were handled. These gaps limit assessment of the result’s role in the original analysis strategy.

Viewed together, the primary and secondary posted summaries share a direction in their group means, while their uncertainty differs. The primary recalculated interval stays below zero; the secondary interval reaches zero. The secondary outcome therefore contributes descriptive context but should not be used to strengthen the primary finding as though it were an independent replication. Both outcomes come from the same small trial and are subject to the same limitations in reporting and analysis detail.

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

• Length of Medication Therapy

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports a two-sided t-test for each of the posted outcome comparisons. The recalculated results use the arm-level means, standard deviations, and participant counts to estimate an unadjusted difference between group means. These are distinct presentations: the registry’s own analysis is the reported analysis, while the recalculation is a simple comparison derived from the posted summary statistics.

What does a mean difference express?

A mean difference subtracts one group mean from the other. In the posted comparison, the standard-therapy-alone group is the reference and the aromatherapy group is the other arm. The primary mean difference is -6.4 days. Its negative direction reflects the lower observed mean in the aromatherapy arm. The units remain days, so the estimate describes an absolute difference in average length of hospitalization, not a relative change.

This kind of contrast is straightforward to interpret when the outcome is continuous and measured on the same scale in both groups. It does not say that every infant in one arm had a shorter stay than every infant in the other. Group means can differ even when individual outcomes overlap substantially. The reported standard deviations provide information about within-arm spread, whereas the uncertainty interval for the mean difference expresses uncertainty about the estimated contrast.

What does the t-test assess?

In general, a t-test evaluates how compatible the observed difference in means is with a null hypothesis of no difference, under the assumptions of the test. A two-sided test considers departures in either direction rather than testing only for a lower or higher mean. The registry reports p=0.03 for the primary analysis and p=0.05 for the secondary analysis. A p-value is not the probability that the null hypothesis is true, nor does it describe the size or importance of a difference. Its interpretation depends on the design and analysis assumptions.

The recalculated p-values are unadjusted comparisons based on the posted summary statistics. The primary recalculation is 0.021. The registry’s reported primary result is p=0.03. The record does not provide the sponsor’s test statistic, analysis dataset, or further model details, so the reported analysis cannot be reconstructed fully from the registry entry alone. The secondary recalculation is 0.05, matching the displayed precision of the reported secondary p-value.

Why does variability matter?

In general, a group mean is estimated more precisely when the observed values vary less and when the group contains more participants, all else being equal. Standard deviations of 10.1 and 6.6 days are reported for the primary outcome. Those values show that lengths of stay varied within both arms. They are not confidence intervals and should not be read as describing the precision of the between-group estimate.

For continuous outcomes, the t-test and the usual mean-difference interval rely on assumptions about how the data behave, particularly for small samples. The registry does not report diagnostic checks, transformations, robust methods, or a model accounting for skewness. Hospitalization duration can be described as a continuous measure for the posted analysis, but the record does not give enough distributional detail to assess whether the analysis assumptions were appropriate. In general, marked skewness or influential observations can affect mean-based inference; the registry does not report whether either issue arose.

Over-dispersion is a concern most often discussed for count outcomes: it means that variability is greater than a model expects, and can make standard errors too small if ignored. Here, the posted primary analysis is a comparison of means for a continuous outcome, and the record does not describe a count model. The specific over-dispersion properties of the outcome are not reported. More generally, selecting a model that matches the outcome’s distribution matters because the model determines how uncertainty is estimated.

What can be inferred from the posted analyses?

The trial is listed as randomized and parallel-group. Random assignment is intended, in general, to make groups comparable at the start of a study, but the registry does not report the sequence-generation or allocation-concealment methods. It also does not report a detailed analysis population, such as whether results were analyzed according to original assignment. The record lists no masking, which is relevant context when interpreting a trial’s conduct and outcome assessment.

The primary outcome is a mean, with standard deviation as its spread measure. The secondary outcome uses the same general summary approach. No adjusted analysis is reported in the registry entry. The recalculated comparisons are unadjusted; they do not account for other variables or for multiple outcome testing. The registry does not report a multiplicity plan, missing-data method, interim analysis, or the original rationale for the chosen enrollment. Those omissions limit the ability to evaluate the full analysis strategy.

In general, statistical significance and precision answer different questions. A p-value summarizes compatibility with a null model under specified assumptions, while a confidence interval gives a range of estimates compatible with the data and method. Neither substitutes for evaluating trial conduct, outcome relevance, and uncertainty about generalizability. The posted record supports a description of the group summaries and the reported tests, but it does not provide all details needed for a comprehensive methodological audit.

11. Confidence Intervals and Precision

The recalculated primary mean difference is -6.4 days, with an interval extending from -11.83 to -0.975 days. The interval is wholly below zero, so the range of values produced by this unadjusted calculation points toward a lower mean length of hospitalization in the aromatherapy arm. The registry’s own reported primary analysis gives p=0.03, but it does not post an estimate or interval for that test. The interval belongs to the recalculation, not to the registry’s reported analysis.

A confidence interval expresses uncertainty in an estimated quantity under the assumptions of the method used. In general, a wider interval indicates less precision than a narrower interval. The interval does not mean that each individual outcome lies within its bounds, and it is not a range of possible individual lengths of stay. Nor should it be interpreted as a probability statement about a fixed true value without specifying a statistical framework.

The primary interval spans values representing different magnitudes of mean difference, so the point estimate should not be treated as exact. The relatively small groups and the observed variation in length of stay are relevant context for that uncertainty. The registry does not report participant-level observations, diagnostic checks, or details of handling missing values, making it impossible to assess their influence on the interval from the record alone.

For the secondary outcome, the recalculated mean difference is -5.3 days, and its interval extends from -10.61 to 0.005 days. That interval reaches zero. This makes the secondary estimate less conclusive as a standalone comparison, even though the observed group means are lower in the aromatherapy arm. The registry reports p=0.05 for its secondary two-sided test. Because this is a secondary result and no multiplicity adjustment is reported, its nominal precision should be interpreted cautiously.

The confidence intervals are not posted as sponsor estimates in the registry record; they are unadjusted recalculations. The record does not specify a confidence level for the intervals. Accordingly, the interpretation focuses on their endpoints and whether they reach zero, without assigning an unreported confidence level.

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 sample-size figures are planning illustrations based on the observed effect, not the original trial’s design assumptions. The registry does not report the original sample-size justification. These illustrations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. For these continuous outcomes, the listed values are participants per arm, not total events.

For the primary outcome, planning for 100% of the observed effect gives 28 participants per arm for 80% power and 38 participants per arm for 90% power. Planning for 75% of the observed effect gives 50 participants per arm for 80% power and 67 participants per arm for 90% power. Planning for 50% of the observed effect gives 112 participants per arm for 80% power and 150 participants per arm for 90% power.

For the secondary outcome, the corresponding values are 39 and 53 participants per arm for planning around 100% of the observed effect; 70 and 93 for 75%; and 156 and 209 for 50%, with each pair referring to 80% and 90% power, respectively.

In general, power is the probability that a planned study will detect an effect of the specified size under its assumptions if that effect is present. The 80% and 90% columns describe different target probabilities for detecting that effect. The curve represents how required sample size changes as the target effect changes under the planning assumptions. Smaller effects require more participants to detect with the same target power. These figures are planning scenarios, not observed power for the completed trial.

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 = -6.400; pooled standard deviation σ = 8.531.
2. n = 2 × (1.96 + 0.842)² × 8.531² / -6.400² = 27.9, rounded up to 28 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 <- -6.4                      # observed difference in means
sigma <- 8.53141254423908                     # 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(3097484)
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 = 28 (80% power), 38 (90% power)
 75% of observed effect: n per arm = 50 (80% power), 67 (90% power)
 50% of observed effect: n per arm = 112 (80% power), 150 (90% power)
power.t.test: 28.9 
Simulated power at n = 28 per arm: 0.788 (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 registry reports the sponsor’s primary analysis as a two-sided t-test with p=0.03. It reports a two-sided t-test with p=0.05 for the secondary outcome. The registry entry does not include the sponsor’s estimated mean differences, confidence intervals, or test statistics, so those details cannot be compared directly with the recalculated estimates.

The unadjusted primary recalculation from the posted arm summaries gives a mean difference of -6.4 days and p=0.021. The unadjusted secondary recalculation gives a mean difference of -5.3 days and p=0.05. These calculations use posted means, standard deviations, and group sizes; they are not a replacement for an analysis based on the trial’s full dataset or a complete statistical analysis plan.

The reported primary p-value and the recalculated p-value are not identical. The registry record does not provide enough analysis detail to establish why their values differ. The results are both presented as reported: the sponsor’s reported test remains the registry analysis, while the recalculation is an independent, unadjusted summary-statistic comparison. The record does not flag a discrepancy between the reported and recalculated results.

No sponsor-reported confidence interval is available in the registry entry. The intervals accompanying the recalculated estimates should therefore not be attributed to the sponsor. Any interpretation of the sponsor analysis beyond its reported test method and p-value would require details not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The registry reports one primary outcome and one secondary outcome. It presents a test for each, but does not report a multiplicity adjustment or a plan for controlling the interpretation of multiple comparisons. In general, testing multiple outcomes can increase the chance of observing a nominally small p-value by chance, especially when each result is treated as a separate confirmatory finding. The absence of a reported adjustment does not show that none was used; it means the approach is not reported in the registry record.

The trial’s analysis population is not reported in the registry record. Although enrollment and arm-level participant counts are listed, the record does not explain whether every randomized participant contributed to each outcome analysis, whether analyses followed original assignment, or whether any participants were excluded. The group counts alone do not answer those questions.

Missing-data handling is also not reported. The entry does not state whether outcome data were complete, how missing hospitalization or medication-duration values were treated, or whether sensitivity analyses were performed. Missing observations can affect a group comparison if their occurrence or treatment differs between arms. Without those details, the impact of missing data cannot be assessed from the registry record.

The record does not report interim analyses, stopping rules, or whether the analysis plan was finalized before outcome data were examined. It also does not report the original sample-size justification or the detailed statistical analysis plan. These details matter because they help distinguish prespecified analyses from decisions made after observing the data and clarify how uncertainty and multiple outcomes were addressed.

The reported method is a two-sided t-test, and the recalculations are unadjusted comparisons of means. No covariate-adjusted model is reported. That does not establish that adjustment was absent from all analyses; it describes what is posted in the registry entry. The entry also lacks diagnostics or sensitivity analyses that would help assess the influence of assumptions about the continuous outcomes.

These reporting gaps do not invalidate the posted summaries, but they limit how fully the analyses can be evaluated. The group means, standard deviations, sample sizes, and reported p-values support a basic description of the outcomes. Stronger claims about the complete analysis strategy, missing observations, multiplicity control, or robustness would require information 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 lists 19 participants at risk for serious adverse events in each arm. It reports zero serious adverse events in the standard-therapy-alone group and zero in the standard-therapy-plus-aromatherapy group. The record also lists 19 participants at risk for other adverse events in each arm and reports zero such events in both groups. Deaths are listed as zero in each arm. No serious adverse event terms are listed.

These figures describe what the registry reports for the recorded safety categories. Zero reported events does not establish that an intervention has no risk, particularly in a trial with 19 participants per arm. Rare or delayed events may not be observed in a study of this size or within the reported follow-up. The record does not provide further information about adverse-event definitions, collection procedures, severity grading, or the period during which events were monitored.

In general, safety counts are most informative when interpreted with the number of participants observed, the duration of observation, and the methods used to collect events. The registry’s at-risk counts provide group denominators, but additional monitoring details are not reported in the registry record. These data should be read as event counts in this trial, not as proof of safety or as a basis for medical advice.

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

The posted results describe a randomized comparison of standard therapy plus lavender and chamomile aromatherapy with standard therapy alone. For the primary outcome, the observed mean length of hospitalization was lower in the aromatherapy arm. The unadjusted recalculation estimates a mean difference of -6.4 days, and its interval lies below zero. The registry separately reports a two-sided primary test with p=0.03.

The results do not show that every infant receiving aromatherapy had a shorter hospitalization, nor do they establish the size of an effect for an individual infant. Group averages do not capture the full distribution of individual outcomes. The interval also indicates uncertainty around the recalculated average difference, and the trial involved 19 participants per arm.

The study compares an additional intervention alongside several components of standard care. It does not isolate the effects of lavender from chamomile, or separate aromatherapy from the surrounding care context. The registry does not report details about the administration schedule or participant-level clinical characteristics that would allow more specific interpretation.

The secondary outcome’s group means follow the same direction as the primary means, but the recalculated interval for medication therapy reaches zero. The secondary result therefore adds context rather than a firm independent confirmation. The registry does not report a multiplicity adjustment, and interpretation of secondary analyses should account for that uncertainty.

The record also does not report missing-data handling, the analysis population, detailed eligibility criteria, or the original sample-size rationale. The unmasked design is relevant context, while the record does not provide information about the methods used to limit possible bias. These limitations restrict conclusions about the robustness and broader applicability of the findings.

Overall, the data show a difference in posted group means for hospitalization, with an unadjusted recalculated interval below zero. They do not by themselves establish the clinical importance, mechanism, or reproducibility of that difference, and they should not be interpreted as medical advice.

18. Why This Trial Matters Statistically

This trial illustrates how a randomized comparison can be summarized with group means, a mean difference, a test, and an uncertainty interval. The primary outcome is expressed in days, so the mean difference retains a direct connection to the measure being studied. Reporting the standard deviations alongside the means also makes within-group variability visible rather than reducing the result to a single contrast.

The registry reports its own two-sided t-test, while the posted summary statistics permit a separate unadjusted recalculation. Keeping those sources distinct is statistically important: a recalculation can provide an estimate and interval when those are absent from the registry’s reported test, but it cannot reproduce all features of an analysis based on the original trial data. The record’s p-values and the recalculated estimate should not be conflated.

The comparison also demonstrates why a secondary endpoint should be interpreted in relation to the primary one and to the study’s testing strategy. The two outcomes share a direction in their posted group means, but the secondary interval reaches zero, and no multiplicity approach is reported. A consistent direction can be informative without being equivalent to independent confirmation.

Finally, the trial shows the value of transparent reporting beyond headline results. Information about missing data, analysis populations, randomization procedures, outcome assessment, and sample-size justification would help readers judge robustness. Those details are not reported in the registry record. Recognizing the distinction between posted results and unreported methodological details is central to responsible statistical interpretation.

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 trial enrolled 38 participants, with 19 in each arm. The modest group sizes mean the estimated group means and their difference may be sensitive to individual observations. The registry does not provide participant-level data or distributional summaries beyond means and standard deviations, so the influence of unusual values or skewness cannot be assessed.

The study is listed as unmasked. The registry does not describe whether outcome assessment or data handling involved safeguards against knowledge of assignment. It also does not report how randomization was generated or whether allocation was concealed. These details would help assess potential sources of bias, but they are not reported in the registry record.

Several analysis details are absent: the analysis population, missing-data methods, the original sample-size rationale, interim analyses, and any multiplicity adjustment. The registry’s reported tests do not include estimates or confidence intervals. The recalculated estimates are unadjusted comparisons from posted summary statistics and cannot substitute for a full participant-level analysis or a complete statistical analysis plan.

The primary outcome timeframe is listed as up to 4 months, but further operational details about determining length of hospitalization are not reported. The record does not provide detailed eligibility criteria, baseline characteristics, or information about the administration and duration of aromatherapy. Those omissions limit assessment of the context in which the findings arose and the extent to which they apply beyond the enrolled participants.

The registry lists zero adverse events in the reported categories, but does not describe event definitions, monitoring duration, or ascertainment procedures. The trial’s size and the unreported safety-monitoring details limit what can be concluded from those counts. These are limitations of the available record and do not, by themselves, establish that a particular bias or problem occurred.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: The Effect of Aromatherapy on Neonatal Abstinence Syndrome and Salivary Cortisol Levels — NCT03097484.
• Registry record last updated 2019-05-14; status last verified 2019-04.
• Results first posted 2019-05-14.
• 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 record describes a completed, randomized, parallel-group, unmasked Phase 3 trial with enrollment of 38 infants with neonatal abstinence syndrome. Standard therapy plus lavender and chamomile aromatherapy was compared with standard therapy alone. Standard care is described as morphine replacement therapy, infant massage, physical therapy, occupational therapy, and music therapy.

The primary outcome was length of hospitalization in days, with length of medication therapy listed as a secondary outcome. Both outcomes were reported as group means and standard deviations for 19 participants per arm. The registry reports two-sided t-tests; unadjusted recalculations provide mean differences and intervals from the posted summaries.

The posted means are lower in the aromatherapy arm for both outcomes. The primary recalculated interval lies below zero, while the secondary interval reaches zero. The registry reports no adverse events in the listed categories. Details about missing data, analysis populations, multiplicity, and the original sample-size rationale are not reported in the registry record.