Effect of Paracetamol on the Common Cold: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Paracetamol on the Common Cold (NCT01277081), a randomized phase 2 study. The primary outcome is Breathing Scores Post 15 Minutes.

2. Clinical Question

The question is narrowly framed around a participant-rated breathing score shortly after dosing. The record also lists cold-symptom and soothing outcomes as secondary measures, but those outcomes do not replace the primary comparison. The registry record does not report a comparison with untreated participants, so the result describes the contrast between the two paracetamol preparations in this study.

3. Trial Design

This was a phase 2, randomized, unmasked, parallel-group study of paracetamol preparations in people with the common cold. The registry lists an enrollment of 200. It lists 100 participants in the mentholated paracetamol hot drink arm and 100 in the paracetamol tablet arm. These are the arm counts recorded for the outcome; they should not be taken as a separately reported count for the defined ITT efficacy population, which required at least one post-baseline efficacy evaluation.

Random allocation is intended to make treatment groups comparable, on average, with respect to participant characteristics that could affect outcomes. It does not guarantee identical groups, and the record does not report details of the allocation sequence or concealment. The study was unmasked, meaning that masking was not used according to the registry entry. For a subjective rating, awareness of the preparation may be relevant when interpreting responses; the record does not describe procedures intended to address that possibility.

The parallel design assigns participants to a treatment group for the study comparison, rather than describing a crossover between preparations. The brief summary identifies a single-dose comparison. The registry record states that the study was completed, with a start in 2010-10 and primary completion in 2010-12. It does not report more detailed visit schedules or dosing instructions.

The primary endpoint was a mean breathing score, with the timeframe described as baseline to 15 minutes. The outcome description says scores were assessed at baseline, 30 seconds, 2, 5 and 15 minutes. The sponsor's reported comparison used repeated measure analysis. The registry record does not report the full statistical plan, the rationale for the enrollment target, or whether any interim analyses were planned or performed.

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: A total of 200 participants were screened and all were randomized into the study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intent to Treat (ITT) Population: All randomized participants who had at least one post-baseline efficacy evaluation.

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 Breathing Scores Post 15 Minutes, measured over Baseline to 15 minutes.

The primary endpoint is the mean breathing score after dosing, with the registry describing the timeframe as baseline to 15 minutes. Participants rated agreement with statements such as “my breathing feels easy,” “I feel airways are open,” and “My nose feels less blocked.” The listed statements also refer to a cooling sensation in the throat, airflow to the lungs, and comfortable breathing. The score is therefore a participant-reported measure of perceived breathing, not a direct physiological measurement.

Each response used a 5 point (0-4) rating scale, with 0 labeled “strongly disagree” and 4 labeled “strongly agree.” For each participant, the registry says a mean was derived by summing the responses and dividing by the number of questions answered. The stated measurement schedule included baseline, 30 seconds, 2, 5 and 15 minutes. The reported primary endpoint title specifies breathing scores post 15 minutes, while the sponsor analysis is described as a repeated measure analysis.

Using a participant-rated score is relevant to a question about the subjective feeling of breathing. It captures how participants reported their experience in response to the listed statements. It does not establish that an objectively measured airway or breathing function changed, and the registry record does not report validation or measurement properties for this score.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean score represent?

A continuous outcome can take values along a measurement scale rather than representing a simple yes-or-no event. The breathing measure is described as a mean of participant responses to several statements. The registry specifies a 5 point (0-4) rating scale and explains that a participant-level mean was formed from answered questions. An arm mean then describes the average score for participants included in that summary. It does not describe every participant's experience, and it can conceal variation among individual scores.

Interpreting a mean depends on the scale's meaning. Here, the statements concern perceived ease, openness, airflow, cooling, congestion, and comfort. More agreement yields a higher response on the described scale. But the record does not provide a minimum clinically important difference, a threshold for improvement, or evidence about how score changes map onto an external measure. The mean difference is thus interpretable as a difference in reported scores, not automatically as a particular degree of physical change or practical benefit.

What does the confidence interval communicate?

A confidence interval expresses uncertainty around an estimate under a statistical procedure and its assumptions. For each arm, the registry reports a mean with a 95% confidence interval. For the sponsor's comparison, it reports an adjusted mean difference with a 95% confidence interval from 0.58 to 0.86. That interval helps convey precision: results compatible with the fitted analysis are concentrated within the reported limits, while the estimate remains uncertain rather than exact.

A confidence interval is not a guarantee that the true value lies within its limits, nor does it describe the range of participant-level scores. The arm-level intervals and the interval for the adjusted difference answer different questions. The latter concerns a model-based contrast; it should not be reconstructed by treating the arm-level intervals as if they were the contrast's own uncertainty calculation.

Why use repeated measure analysis?

The outcome description lists measurements at baseline, 30 seconds, 2, 5 and 15 minutes. Measurements from the same participant are related, so an analysis that treats all observations as unrelated would generally fail to reflect that dependence. Repeated measure methods are designed to analyze outcomes measured over time while accounting for correlation among observations from the same participant. They can estimate treatment contrasts using the pattern of observations, depending on the model and its specified terms.

The registry identifies the sponsor's method as “Repeated Measure Analysis” and labels its result an adjusted mean difference. It does not describe the model formula, covariance structure, adjustment variables, treatment-by-time terms, or handling of incomplete repeated measurements. Those details matter for understanding precisely how the adjusted estimate was formed. The registry record does not report them, so the analysis cannot be fully reproduced from the information posted.

How should the p-value be read?

The sponsor reports p < 0.001 for the primary comparison. In general, a p-value assesses how unusual the observed data, or data more extreme, would be under a specified null model. A small p-value can be evidence against that null model, provided the model and analysis are appropriate. It is not the probability that the null hypothesis is true, and it does not quantify the size or practical importance of the score difference. The registry record does not report whether this p-value was adjusted for testing multiple outcomes or time points.

What does the planned sample-size information mean?

The registry's planning assumptions describe illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. They describe detecting a stated fraction of the observed effect. Such calculations are planning illustrations: they explore sample-size requirements under stated assumptions and do not measure the study's achieved power after the data are observed. The registry record does not report the original design calculation or its assumptions, and no planning result should be read as proof that the completed study had a particular probability of detecting an effect.

In general, power is a property of a design under assumed conditions, not a measure of whether a finding is reliable after results are known. Planning from an observed effect can also be sensitive to the estimated effect. The posted assumptions therefore help characterize the calculation's purpose but do not establish the trial's prespecified target or the adequacy of its design.

What does the unmasked design imply for measurement?

Randomization addresses allocation to groups, while masking concerns awareness of group assignment. The registry states that masking was none. Because the endpoint is based on participants' reports about how breathing feels, awareness of which preparation was received could be relevant to responses. This is a consideration in interpreting the outcome, not evidence that responses were biased. The record does not report additional safeguards or an assessment of expectation effects.

10. Analyses Reported by the Sponsor

The sponsor reports an adjusted mean difference of 0.72, with a 95% confidence interval from 0.58 to 0.86 and p < 0.001. The method is identified as repeated measure analysis. This is the sponsor's own inferential analysis of the primary outcome and is the relevant posted result for the adjusted group comparison.

The arm summaries are 0.83 for the mentholated paracetamol hot drink and 0.11 for the paracetamol tablet, each reported with its own 95% confidence interval. They are summaries of the groups, not a substitute for the adjusted repeated-measure comparison. Differences between an adjusted model estimate and a simple contrast of arm summaries can arise because they represent different analyses. The registry record does not give enough model detail to reproduce the adjusted estimate independently.

No independent two-arm recalculation is reported as estimable for this continuous endpoint. There is therefore no recalculated estimate to compare with the sponsor's result, and the record does not flag a discrepancy. The sponsor's result should be described as the posted model-based analysis; it should not be presented as independently verified from the arm means alone.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 6 outcome measures, including the primary breathing score and 5 secondary outcomes: breathing score post 60 minutes, cold symptoms score post 15 minutes, cold symptoms score post 60 minutes, soothing attribute scores, and overall cold symptoms score. It also lists 4 analyses. The presence of several outcomes and time points raises a general multiplicity question: when many statistical tests are conducted, the chance of observing at least one small p-value can increase if each test is treated separately.

The record does not report a multiplicity adjustment, a prespecified testing hierarchy, or a statistical plan describing how conclusions across endpoints were controlled. The primary result should therefore be distinguished from findings on secondary measures, and the posted p-value should not be assumed to account for testing beyond the primary comparison. The record does not provide enough information to determine how outcome selection or reporting was handled.

The primary analysis population is defined as randomized participants with at least one post-baseline efficacy evaluation. This is the registry's stated ITT population definition. It is not identical, in wording, to a definition that necessarily includes every randomized participant regardless of whether post-baseline data are available. The record does not report the number meeting this definition or how many were missing outcome measurements.

Handling of missing measurements is important for a repeated measure analysis, because incomplete observations may affect which data contribute and how the model estimates the contrast. The registry record does not report the missing-data method, reasons for missingness, sensitivity analyses, or whether participants were excluded from particular timepoint summaries. No assumption about those procedures can be made from the posted outcome definition alone.

12. 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 1% reporting threshold.

For the mentholated paracetamol hot drink arm, the registry lists 0 participants affected by serious adverse events among 100 at risk and 0 affected by other adverse events among 100 at risk. For the paracetamol tablet arm, it likewise lists 0 affected by serious adverse events among 100 at risk and 0 affected by other adverse events among 100 at risk. No serious adverse event terms are listed.

These entries describe the adverse-event counts reported in the registry; they do not establish that no events of any kind occurred outside the registry's definitions, observation period, or reporting process. The record does not report the observation duration for adverse events or further details about collection and classification. Death counts are not reported in the registry record.

Zero reported events in these groups should not be interpreted as proof that an event cannot occur or that the preparations are risk-free. The counts are also not a comparison capable of establishing a safety difference. They are a limited description of the events recorded for the study groups, and the absence of listed serious-event terms means only that no such terms appear in this record.

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

The posted primary result is a statistically clear difference in participant-rated breathing scores between the two study groups under the sponsor's repeated measure analysis. The arm means are higher for the mentholated paracetamol hot drink group than for the paracetamol tablet group, and the adjusted mean difference is positive with a 95% confidence interval that does not include zero. The reported p-value is p < 0.001. Together, these figures describe the direction, estimated size, and statistical precision of the reported comparison.

That result does not by itself establish the clinical importance of the score difference. The registry does not report a threshold for a meaningful change, and the endpoint is a subjective rating rather than an objective measure of breathing. Statistical evidence against a null difference is not the same as evidence that participants experienced a difference of a particular practical magnitude.

The comparison also does not show how either preparation compares with placebo, no treatment, or another class of intervention. Both listed groups received paracetamol preparations, and the study's stated focus was their subjective effects following a single dose. The result pertains to this comparison and this endpoint; it cannot establish effects on all common-cold symptoms or outcomes not reported.

Interpretation is further bounded by the unmasked design and limited information on model specification, missing-data handling, and multiplicity. These are uncertainties in the record, not proof that the finding is invalid. The record's statistical result should be read alongside those limits, without turning it into a general claim about treatment efficacy or safety.

14. Why This Trial Matters Statistically

This study illustrates why the definition of an endpoint matters as much as the numerical result. “Breathing score” might sound like a direct measure of respiratory function, but the registry describes a mean of participants' ratings of agreement with statements about perceived ease, openness, airflow, congestion, cooling, and comfort. Statistical interpretation depends on recognizing that distinction. The analysis concerns reported experience on a rating scale.

It also illustrates the difference between an arm-level summary and a model-adjusted comparison. The registry reports means for each preparation and separately reports a repeated measure adjusted mean difference. Those quantities are related to the same clinical question but arise from different summaries. A reader should not treat the arm means as a complete reconstruction of the repeated-measure model.

The repeated schedule makes correlation important: each participant contributes ratings at multiple times, and those responses are not necessarily independent. A repeated measure method is a relevant class of analysis for such data, but the registry's brief method label does not reveal its full assumptions. This makes transparent reporting of the model, missing-data method, and analysis population important for reproducibility.

Finally, the record shows how statistical strength and clinical interpretation are distinct. The reported confidence interval and p-value characterize evidence under the sponsor's model, while the record does not identify a meaningful-change threshold for the score. The result can be statistically precise yet still require careful judgment about what the scale captures and how far the conclusion applies.

15. 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 endpoint is subjective and the study was unmasked. Participants' ratings may be influenced by their perceptions of the preparation, though the registry does not establish that this occurred. The score combines responses to several statements about breathing, and the record does not report validation evidence, a meaningful-change threshold, or an interpretation guide for the resulting mean.

The sponsor reports repeated measure analysis, but the registry does not describe the model specification or adjustment variables. It also does not report the method for handling missing repeated measurements. Those omissions limit independent reproduction of the adjusted mean difference and assessment of the assumptions behind its confidence interval and p-value.

The record defines the ITT efficacy population as randomized participants with at least one post-baseline efficacy evaluation but does not state the number meeting that definition. It does not report missingness by group or timepoint. The listed arm counts therefore should not be assumed to show the number contributing to every part of the primary analysis.

Several secondary outcomes and multiple analyses are listed, but the registry does not report a multiplicity strategy or a prespecified hierarchy for interpreting tests. The record also does not give the original sample-size rationale or full protocol-based statistical plan. The planning assumptions described in the record are illustrations based on the observed effect, not evidence of the original design basis or achieved power.

Finally, the active-comparator design does not estimate either preparation's effect relative to placebo or no treatment. The reported timeframe is short, and the record does not report longer-term outcomes. These limits constrain interpretation to the comparison and outcomes recorded, rather than establishing broader effects for people with the common cold.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Paracetamol on the Common Cold — NCT01277081.
• Registry record last updated 2015-02-18; status last verified 2013-06.
• Results first posted 2015-02-18.
• 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.

19. Record Summary

The registry record describes a completed phase 2 randomized, unmasked, parallel-group study of a paracetamol hot drink and paracetamol tablets for the common cold. Enrollment is listed as 200, with 100 in each outcome arm. The primary endpoint is a participant-rated mean breathing score, with a baseline-to-15-minute timeframe.

The sponsor reports a repeated measure adjusted mean difference of 0.72, with a 95% confidence interval from 0.58 to 0.86 and p < 0.001. Arm-level mean scores are 0.83 for the hot drink group and 0.11 for the tablet group. The record also lists 5 secondary outcomes and reports zero participants affected by serious or other adverse events in each group.

Important details are not reported in the registry record, including the full model specification, missing-data handling, multiplicity strategy, and an interpretation threshold for a meaningful score change. The result is a model-based comparison of subjective breathing scores for the two preparations, not a comparison with placebo or no treatment.