This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Grass Pollen Allergen Immunotherapy Tablet (AIT) Time Course Study (NCT02005627), a randomized phase 2 study. The primary outcome is Total Nasal Symptom Score After Nasal Allergen Challenge (NAC).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02005627 |
| Phase | Phase 2 |
| Condition | Allergic Rhinitis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 46 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Imperial College London |
| Results posted | Yes |
2. Clinical Question
Population
The registry identifies the condition as allergic rhinitis and describes a study of seasonal rhinitis associated with grass pollen. The primary outcome was assessed after a grass pollen nasal allergen challenge following treatment. Further eligibility criteria, participant characteristics, and details about the severity or history of participants’ symptoms are not reported in the registry record.
Intervention
The active arm received Grazax, a grass pollen allergen immunotherapy tablet taken once daily. The registry describes the tablet as an oral lyophilisate containing 75,000 SQ-T. Treatment was assessed after 12 months.
Comparator
The comparison was Grazax placebo, also taken once daily. The registry describes the placebo as having the same composition as the active tablet except that it excluded the grass pollen allergen extract.
Primary question
The primary question was whether the total nasal symptom score 60 minutes after nasal allergen challenge differed between the active-treatment and placebo arms after 12 months of treatment. The score ranges from 0 to 12, with higher scores indicating more severe symptoms. The registry reports lower mean scores in the Grazax arm and a two-sided t-test with p < 0.05. The reported primary comparison estimate and its confidence interval are not reported in the registry record.
3. Trial Design
This was a phase 2, randomized, quadruple-masked, parallel-group study sponsored by Imperial College London. The registry lists an enrollment of 46. For the primary outcome, the posted results include 23 participants in the Grazax arm and 23 in the Grazax Placebo arm. The registry records the study as completed. It lists a start date of 2013-09-01 and a primary completion date of 2017-03-01.
The active intervention was Grazax, a grass pollen allergen immunotherapy tablet taken once daily. The comparator was a matching placebo taken once daily, described as differing from the active tablet by the absence of grass pollen allergen extract. The study’s parallel-group structure means participants were assigned to an active-treatment or placebo arm rather than being described as crossing between treatments. The registry identifies randomization and quadruple masking but does not report further details about the randomization procedure or who was masked.
The primary outcome was the total nasal symptom score after nasal allergen challenge, assessed 60 minutes after challenge following 12 months of treatment. Secondary outcomes included early and late phase intradermal tests, change from baseline in delta peak nasal inspiratory flow, and end-of-season global rhinitis symptoms. Results are posted for three secondary outcomes; results for change from baseline in delta peak nasal inspiratory flow are not reported in the registry record.
The registry does not report the planned sample-size justification, the allocation ratio as a protocol detail, treatment adherence, or a detailed schedule of assessments. Those omissions limit what can be said about the design beyond the recorded randomized, masked, parallel comparison and the posted outcome descriptions.
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
| Stage | Grazax | Grazax Placebo |
|---|---|---|
| STARTED | 23 | 23 |
| COMPLETED | 21 | 19 |
| NOT COMPLETED | 2 | 4 |
Reasons for not completing this period:
| Reason | Grazax | Grazax Placebo |
|---|---|---|
| Lost to Follow-up | 1 | 2 |
| Withdrawal by Subject | 1 | 2 |
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.
| Characteristic | Unit | Grazax | Grazax Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 23 | 23 | 46 | |
| Age, Continuous | years | 31.5 (SD 2.12) | 36.9 (SD 1.97) | 34.2 (SD 2.04) |
| Sex: Female, Male: Female | Participants | 10 | 5 | 15 |
| Sex: Female, Male: Male | Participants | 13 | 18 | 31 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: United Kingdom | participants | 23 | 23 | 46 |
| Specific Immunoglobulin E (IgE) | kU/l | 14.4 (SD 3.12) | 14.17 (SD 2.81) | 14.28 (SD 2.96) |
6. Primary Endpoint
The registry lists the primary outcome as Total Nasal Symptom Score After Nasal Allergen Challenge (NAC), measured over 60 minutes post-challenge after 12 months of treatment.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the total nasal symptom score measured 60 minutes after a grass pollen nasal allergen challenge, after 12 months of treatment. It is a continuous measure on a scale from 0 to 12, with higher scores representing more severe symptoms. A numerical score allows the average symptom response after challenge to be compared between the Grazax and placebo arms.
The challenge provides a defined context for measuring nasal symptoms rather than relying only on an unspecified report of symptoms across a season. The score is intended to capture the severity of the nasal response at the stated post-challenge assessment. The registry does not describe the individual symptom components, scoring instructions, validation, or the reason this endpoint was selected over other possible measures. Those details are not reported in the registry record.
The posted arm means are 3.37 for Grazax, with a 95% confidence interval from 2.7 to 4.05, and 4.71 for Grazax Placebo, with a 95% confidence interval from 4.0 to 5.4. The sponsor reports a two-sided t-test with p < 0.05 for the primary comparison, but the comparison estimate and its confidence interval are not reported in the registry record. The arm-specific confidence intervals describe uncertainty around each mean; they do not by themselves give the uncertainty around the difference between arms.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary outcome is the mean total nasal symptom score after challenge. The posted mean is 3.37 in the Grazax arm and 4.71 in the placebo arm. Since higher scores indicate more severe symptoms, the observed arm means place the Grazax group lower on this scale at the stated assessment. The registry also reports a two-sided t-test result of p < 0.05 for the primary comparison. This is evidence against equal means under the test’s assumptions, but it does not quantify the size or precision of the difference by itself.
The arm-specific 95% confidence intervals are 2.7 to 4.05 for Grazax and 4.0 to 5.4 for placebo. A confidence interval gives a range of values compatible with the data under the method used; it is not a range containing a known fixed proportion of individual participants’ scores. These intervals relate to each arm mean, not the difference between means. A primary contrast estimate and confidence interval are not reported in the registry record, so the precision of the between-arm difference cannot be read directly from the posted primary results.
The primary comparison is the main basis for interpreting this study’s stated question. The reported p-value indicates that the sponsor’s test met the conventional significance threshold described by its result, but it does not state how large a difference is important to participants or how much uncertainty remains about the magnitude. The registry does not report a threshold for clinical importance or further context for interpreting score changes. Statistical evidence and clinical importance are different questions.
The secondary outcomes add context about other nasal, cutaneous, and symptom measures. The posted secondary summaries generally show lower means in the Grazax arm, while the recalculated evidence varies across measures. Those secondary comparisons are unadjusted and should be treated as exploratory unless a prespecified analysis plan and multiplicity approach are available. The registry record does not report such an approach.
These findings describe the posted outcomes for this randomized study. They do not establish how results would generalize to people outside the study, and the record lacks participant characteristics and several details needed to assess representativeness. Nor do the results alone determine how a treatment should be used. The interpretation is limited to the measured scores, the reported comparison, and the uncertainty and missing details in the registry record.
9. Statistical Methods Explained
The primary outcome is a continuous score, and the registry reports an arm mean and a 95% confidence interval for each group. A mean describes the central level of the recorded scores in that arm. A confidence interval expresses uncertainty about the estimated mean under the statistical method used. It does not describe the full spread of individual participant scores, and it is not the same as an interval for the treatment contrast.
What does the primary p-value tell us?
The sponsor reports a two-sided t-test for the primary comparison, with p < 0.05. A two-sided test evaluates evidence for a difference in either direction rather than only a difference in a prespecified direction. A p-value describes how unusual data at least as incompatible with the null hypothesis would be if the null hypothesis and the test assumptions held. It is not the probability that the null hypothesis is true, nor does it measure the probability that the result will replicate. The registry does not provide the test statistic, an exact p-value, or a primary contrast estimate and confidence interval.
The primary arm means and confidence intervals permit description of each group’s observed average, but they do not supply the missing contrast interval. The sponsor’s reported test is therefore the available inferential result for the primary comparison. The recalculated primary comparison is not available because the registry record does not contain values that are reported as estimable for that calculation.
How should the recalculated secondary contrasts be read?
For the secondary continuous outcomes with posted arm means and standard errors, the recalculations are simple, unadjusted comparisons based on the summary statistics. The mean difference is expressed as Grazax minus Grazax Placebo. A negative value therefore corresponds to a lower mean in the Grazax arm. These recalculations are not the sponsor’s analyses and do not replace a prespecified adjusted analysis.
A confidence interval for a mean difference describes the uncertainty around that estimated contrast under the calculation’s assumptions. If the interval includes zero, the data are compatible with no mean difference as well as with values on either side of zero at the confidence level used. If the interval does not include zero, that is evidence against a zero difference under that calculation, but it does not establish clinical importance. The recalculated secondary intervals and unadjusted p-values should be read as descriptive statistical comparisons, especially because the registry does not report a multiplicity plan.
Standard errors describe uncertainty in an estimated mean, rather than the spread of individual observations. The registry gives standard errors for the secondary arm means. A standard deviation instead describes variability among individual observations. The recalculation uses the posted standard errors to obtain the pooled standard deviation and standardized effect listed with each comparison; these are derived quantities, not separately reported trial outcomes. Such standardization can help compare effects expressed in different measurement units, but it does not make different outcomes clinically interchangeable.
Why does over-dispersion matter?
General statistical explanation: over-dispersion occurs when observed variability is greater than a model or analysis assumes. When that happens, uncertainty can be understated, making confidence intervals too narrow and tests too likely to suggest evidence of a difference. The outcomes in this study are continuous, and the registry does not report an over-dispersion assessment or a model-based adjustment for it. It would therefore be inappropriate to claim that over-dispersion was present or that a particular correction was used.
More generally, the reliability of a mean comparison depends on the data and assumptions behind the analysis, including how observations were collected and whether the analysis accounts for the study design. The registry identifies a t-test for the primary comparison, but does not report its diagnostic checks or handling of departures from assumptions. Details of the analysis plan beyond the posted result are not reported in the registry record.
What do the planning illustrations mean?
The planning illustrations use the observed secondary effects as a starting point and consider detecting a stated fraction of those effects. Their assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The reported quantities are participants per arm for 80% power and participants per arm for 90% power. They are hypothetical planning illustrations, not the trial’s design justification and not observed power.
Observed power is not a useful substitute for interpreting the estimated effect and its uncertainty: after a study is complete, it largely reflects the observed result. The planning values instead indicate how sample-size requirements would change under the stated assumptions if a future study aimed to detect the specified fraction of the observed effect. They depend on the observed effect, which may be imprecise, and should not be treated as a guarantee of future performance. The trial’s own sample-size justification and protocol assumptions are not reported in the registry record.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| t-test, 2 sided | not reported | < 0.050 |
For the primary outcome, the sponsor reports a two-sided t-test with p < 0.05. The registry also posts the mean and 95% confidence interval within each arm. It does not report the sponsor’s primary mean-difference estimate, the confidence interval for that difference, or an exact p-value. The primary comparison therefore cannot be compared numerically with an independently recalculated contrast using the posted primary summaries.
The registry record does not contain values reported as estimable for a two-arm recalculation of the primary continuous outcome. Accordingly, no recalculated primary contrast is presented. This is not a competing analysis result: it reflects the absence of a usable comparison estimate in the registry record. The sponsor’s reported test remains the available inferential result for the primary endpoint.
For the secondary outcomes, some recalculated unadjusted contrasts can be obtained from the posted means and standard errors. The early- and late-phase intradermal outcomes do not have sponsor-reported comparison results in the registry record. The end-of-season global symptom outcome has a posted superiority analysis label, but its method, estimate, confidence interval, and p-value are not reported. Consequently, the recalculations cannot be checked against a complete sponsor-reported secondary analysis. The registry does not report enough detail to assess whether the sponsor used additional adjustment or other analysis methods.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome and four secondary outcomes. Results are posted for three secondary outcomes; change from baseline in delta peak nasal inspiratory flow is listed but its results are not reported in the registry record. The registry does not describe a hierarchy among outcomes, identify which secondary comparisons were confirmatory, or report a multiplicity adjustment. It is therefore not possible to determine whether the sponsor controlled the overall false-positive risk across the outcomes or whether the secondary tests were intended to be interpreted as exploratory.
Multiplicity matters because each additional statistical test creates another opportunity to observe a result that appears unusual under a null hypothesis. A correction or prespecified testing hierarchy can address that issue, but the suitable approach depends on the analysis plan and scientific aims. The registry does not report enough information to establish which approach, if any, was planned or used. The recalculated secondary p-values are unadjusted and should not be interpreted as if they account for testing across outcomes.
Missing-data procedures are not reported in the registry record. The record does not explain how missing outcome measurements were handled, whether any participants were excluded from particular analyses, or whether sensitivity analyses were performed. The analysis population for the primary and secondary outcomes is also not reported. The outcome-level arm counts are stated, but the record does not identify whether analyses followed an intention-to-treat approach or another population definition.
The registry does not report interim analyses, stopping rules, or a detailed statistical analysis plan. It also does not report the trial’s sample-size justification. The planning illustrations based on observed effects are separate from those protocol details and cannot establish what sample size was planned before the study. These omissions limit assessment of prespecification, selective reporting, and the handling of incomplete data. They do not establish that any particular analysis procedure was or was not used; they mean that the relevant information is not reported in the registry record.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Grazax | 0 | 23 | 0.0% |
| Grazax Placebo | 0 | 23 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Grazax | 0 of 23 |
| Grazax Placebo | 0 of 23 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Grazax | 22 of 23 |
| Grazax Placebo | 20 of 23 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Grazax | Grazax Placebo |
|---|---|---|---|
| Common cold/URTI | Infections and infestations | 15 of 23 | 20 of 23 |
| Allergic Reaction | Immune system disorders | 19 of 23 | 3 of 23 |
| Headache | Nervous system disorders | 5 of 23 | 5 of 23 |
| Dyspepsia | Gastrointestinal disorders | 6 of 23 | 0 of 23 |
| Vomiting | Gastrointestinal disorders | 4 of 23 | 0 of 23 |
| Mucositis oral | Gastrointestinal disorders | 1 of 23 | 1 of 23 |
| Tooth ache | General disorders | 2 of 23 | 0 of 23 |
| Abdominal pain | Gastrointestinal disorders | 1 of 23 | 0 of 23 |
For serious adverse events, the registry reports zero affected participants in the Grazax arm and zero in the Grazax Placebo arm. Each arm has 23 participants listed as at risk for the serious-adverse-event summary. The registry reports no deaths in either arm. These figures describe the posted safety counts; they do not establish that the risk of a rare or unobserved event is absent.
For other adverse events, the registry reports 22 affected participants in the Grazax arm and 20 in the placebo arm, with 23 at risk in each arm. The summary does not provide event-specific descriptions for these other adverse events, so their types, severity, duration, and relationship to treatment cannot be assessed from these counts alone. Serious adverse event terms are not reported in the registry record.
Safety counts should be read alongside the period and methods used to collect them. The registry record does not provide further detail about ascertainment, follow-up completeness, or how adverse events were classified. These counts are descriptive and should not be interpreted as a complete safety profile or as a direct comparison of event risk beyond what the posted summaries state.
13. What the Result Does, and Does Not, Mean
The primary results show that the posted mean nasal symptom score after challenge was lower in the Grazax arm than in the placebo arm, and the sponsor reports a two-sided primary test with p < 0.05. The score’s direction is defined in the registry: higher values mean more severe symptoms. This supports a description of the observed group results at the stated assessment, after 12 months of treatment.
The result does not provide the size and precision of the primary between-arm difference, because the registry does not report a contrast estimate or confidence interval. The separate arm confidence intervals cannot replace that missing contrast interval. The p-value alone does not express clinical importance, certainty of replication, or the probability that the treatment caused a particular outcome in an individual.
The secondary outcomes provide additional measurements with generally lower means in the Grazax arm, but they are not all equally precise and the registry does not report how multiplicity was handled. One listed secondary outcome lacks posted results. These features mean the secondary data should be interpreted as supporting context rather than definitive evidence for every measured outcome.
The record does not report participant characteristics, detailed eligibility criteria, missing-data methods, analysis populations, or a full statistical analysis plan. It is therefore difficult to assess how representative the participants were, how incomplete observations may have affected estimates, or whether all analyses followed a prespecified plan. The results cannot on their own establish generalizability beyond the studied setting or settle questions not measured by these outcomes.
These statistical findings are not medical advice. They describe recorded group averages, uncertainty where reported, and limitations in the registry record. Decisions about treatment require information beyond these summary results, including individual circumstances and evidence not assessed by this study record.
14. Why This Trial Matters Statistically
This study illustrates why the distinction between an arm mean and a treatment contrast matters. The registry gives a mean and confidence interval for each primary-outcome arm, along with a sponsor-reported test result. Yet it does not report the primary difference estimate or its confidence interval. Readers can describe the direction of the observed means and the reported test, but cannot directly assess the precision of the primary contrast from the arm summaries alone.
It also shows how secondary outcomes can contribute a broader picture without having equal evidential status. The outcomes measure different responses, and the unadjusted recalculations vary in precision. Without a reported multiplicity strategy, a collection of secondary p-values should not be read as a single confirmatory body of evidence. Prespecified analysis plans and transparent reporting are important for distinguishing confirmatory findings from exploratory patterns.
The planning illustrations demonstrate another essential distinction: sample-size planning is not observed power. Illustrations based on observed effects can help explore future study sizes under explicit assumptions, but they do not reveal the trial’s original design rationale. Here, the registry does not report the trial’s own sample-size justification, so the retrospective planning values cannot fill that gap.
Finally, the study emphasizes that clinical outcome reporting and statistical reporting are complementary. The scale’s range and direction make the outcome interpretable, while the missing contrast interval, unspecified analysis populations, and unreported missing-data and multiplicity methods constrain precision and robustness. Transparent reporting of estimates, uncertainty, and analysis decisions is necessary for a full statistical appraisal.
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.
Several limitations are specific to the information available for this trial. The primary comparison has a reported p-value, but the registry does not report the mean-difference estimate or its confidence interval. This restricts assessment of the magnitude and precision of the primary contrast. The arm-specific means and intervals do not resolve that limitation.
The study enrolled participants with allergic rhinitis, but additional eligibility criteria and participant characteristics are not reported in the registry record. Without these details, the population represented by the results cannot be described more specifically, and generalizability cannot be assessed in depth. The registry’s background description concerns seasonal grass pollen rhinitis, but it does not supply a detailed account of participants’ clinical profiles.
The record does not report analysis populations, missing-data procedures, or the treatment of participants with incomplete outcomes. It also does not provide a full statistical analysis plan, an explanation of multiplicity handling, or a sample-size justification. These missing details limit assessment of potential bias, prespecification, and the reliability of secondary inferences.
Results are not posted for one listed secondary outcome, change from baseline in delta peak nasal inspiratory flow. The available secondary summaries therefore do not cover every outcome named in the registry. For the end-of-season global symptom outcome, the registry lists a superiority analysis but does not provide the sponsor’s method, estimate, confidence interval, or p-value. The recalculated secondary comparisons are unadjusted and should not be treated as a substitute for unavailable sponsor analyses.
Safety reporting is also limited to summary counts. Event-specific details for other adverse events and serious adverse event terms are not reported in the registry record. Follow-up and ascertainment details are not reported, limiting interpretation of the safety summaries.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Grass Pollen Allergen Immunotherapy Tablet (AIT) Time Course Study — NCT02005627.
- Registry record last updated 2019-12-04; status last verified 2019-11.
- Results first posted 2019-12-04.
- 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.
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19. Record Summary
The registry describes a completed phase 2, randomized, quadruple-masked, parallel-group study sponsored by Imperial College London. It compared once-daily Grazax with once-daily Grazax placebo in allergic rhinitis. The primary outcome was total nasal symptom score 60 minutes after grass pollen nasal allergen challenge following 12 months of treatment.
The primary arm means were 3.37 for Grazax and 4.71 for placebo; higher scores indicate more severe symptoms. The sponsor reports a two-sided t-test with p < 0.05, but the primary contrast estimate and confidence interval are not reported in the registry record. Three secondary outcomes have posted results, with generally lower means in the Grazax arm; recalculated secondary comparisons are unadjusted. Results for one listed secondary outcome are not reported.
The record also lists no serious adverse events affecting participants and no deaths in either arm, alongside other adverse-event counts. Important details—including the sample-size justification, analysis populations, missing-data procedures, and multiplicity plan—are not reported in the registry record.