The ATTAIN Study: A Therapeutic Trial of Afatinib In the Neoadjuvant Setting: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The ATTAIN Study: A Therapeutic Trial of Afatinib In the Neoadjuvant Setting (NCT02271906), a na phase 2 study. The primary outcome is Number of Patients With Treatment "Completed".

2. Clinical Question

In practical terms, the study was designed to examine whether patients could proceed through a preoperative course of afatinib and the specified surgical and postoperative milestones. The brief summary identifies tolerability and safety as aims. The primary endpoint is a defined completion count, not a direct measure of tumor response, survival, or comparative treatment effect. The registry lists a secondary outcome concerning change in standard uptake value from preoperative to postoperative PET-CT, but it does not give an analysis result for that outcome. The question the available record can answer is therefore limited: it describes what was planned and gives some safety counts, but it does not establish how many participants met the completion criteria or what happened to the secondary measure.

3. Trial Design

The ATTAIN Study is registered as a phase 2 therapeutic trial in a neoadjuvant setting for lung cancer. Its model is single group. Allocation is listed as NA, and masking as NONE. These entries describe a study without a randomized comparison arm and without masking, rather than a controlled comparison in which treatment assignment or assessment is concealed.

The intervention is listed as BIBW 2992, a drug identified as afatinib in the study title and brief summary. The arm description calls for 40 mg by mouth daily for a minimum of 14 days and until the day of surgery. The brief summary says the research goal was to learn whether it was tolerable for patients with NSCLC to receive afatinib before surgery and to study safety.

The primary outcome is the number of participants whose treatment was declared completed. Its timeframe runs from the start of neoadjuvant treatment to 30 days of postoperative care. The definition combines treatment exposure, surgery, and postoperative follow-up: at least 14 days of neoadjuvant treatment, thoracotomy for the planned surgical resection, and 30 days of postoperative care are all required.

The record lists enrollment as 2 and status as TERMINATED. The recorded study start is 2015-07-01, and the primary completion date is 2017-08-16. The reason for termination is not reported in the registry record. No randomized allocation, comparator arm, blinding procedure, or analysis records are listed. Details such as eligibility criteria, the reason for choosing the planned enrollment, and the operational meaning of termination are not reported in the registry record, so they cannot be inferred from these design entries.

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: Following registration, patients should begin protocol treatment within 2 weeks. If a patient does not receive protocol therapy within 2 weeks following registration, the patient's registration on the study may be canceled at the discretion of the study investigators and the patient will be considered a screen failure.

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 Number of Patients With Treatment "Completed", measured over From the start of neoadjuvant treatment to 30 days post operative care.

The primary endpoint is a count of participants meeting a prespecified definition of treatment completion. A participant qualifies only if they complete at least 14 days of neoadjuvant treatment, undergo thoracotomy for the planned surgical resection, and complete 30 days of postoperative care. The stated timeframe begins with neoadjuvant treatment and extends through the postoperative period.

This kind of endpoint can summarize whether participants pass through a sequence of treatment and care milestones. It is relevant to a preoperative study because the intervention is intended to occur before planned surgery, and completion is defined to include both treatment and surgical follow-through. It is not simply a measure of taking the drug for a specified duration: the surgery and postoperative-care conditions are also part of the endpoint definition.

As a general statistical point, a count endpoint can be informative about the number of participants meeting a rule, but interpretation depends on the rule being applied consistently and on the count being reported with its denominator and uncertainty. The registry record defines the rule but contains no analysis result for the primary endpoint. It therefore does not state how many participants completed treatment, nor does it provide a completion proportion or an interval expressing its precision. The endpoint definition alone cannot establish whether the planned treatment course was tolerable or whether any clinical benefit occurred.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies the primary outcome as a participant count, with a binary meaning: participants either meet the completion definition or do not. The definition requires at least 14 days of neoadjuvant treatment, thoracotomy for the planned surgical resection, and 30 days of postoperative care. These are endpoint criteria, not evidence that any participant met them. The registry contains no analysis records, so no observed completion count or analysis of this outcome is listed.

What does a count endpoint tell the reader?

As a general statistical explanation, a count of participants meeting a binary rule can be presented on its own or alongside the number assessed. The accompanying denominator matters because the same count can have different meanings in groups of different sizes. An estimated proportion describes the share meeting the rule, while a confidence interval describes the range of values reasonably compatible with the data under the analysis assumptions. A narrow interval indicates greater precision; a wide interval indicates more uncertainty. These concepts do not supply missing trial results: the registry record does not report a completion count, proportion, denominator for an outcome analysis, or confidence interval.

For very small datasets, estimates of proportions can be unstable, and standard large-sample approximations may not perform well. Exact or other small-sample methods may be considered in general, depending on the analysis plan and data. The method used for the primary endpoint is not reported in the registry record. It would therefore be inappropriate to attribute a particular interval method, test, or model to this study.

What does the single-group design allow?

As a general explanation, a single-group study can describe outcomes among participants who received the intervention, subject to how those participants were selected and how outcomes were measured. It does not include a concurrent comparator for estimating a between-group treatment effect. Without such a comparator, an observed outcome cannot be attributed to the intervention by contrasting it with what would have happened under another treatment. In this trial, the record explicitly lists a single-group model, allocation as NA, and masking as NONE. No adjustment method or causal analysis is reported.

How should the safety counts be read?

The record lists separate figures for participants at risk and affected for serious and other adverse events, as well as a deaths count. These are descriptive entries. A count does not show the event's timing, duration, severity beyond the serious/non-serious categorization, clinical course, or whether investigators judged it related to the drug. The record does not list top serious adverse event terms. It also does not explain how adverse events were collected or coded. General statistical interpretation of safety data would consider these details and the completeness of follow-up, but those details are not reported in the registry record.

What do the planning assumptions mean?

The planning note describes an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. For time-to-event outcomes it specifies total events using the Schoenfeld approach; for other outcomes it specifies participants per arm. These are planning conventions, not evidence that the ATTAIN trial used a two-arm design: the trial itself is recorded as single group. The note also states that such sample-size calculations are illustrations rather than the trial's own design, and they are not observed power. No trial-specific sample-size justification or statistical plan is reported in the registry record.

As a general principle, sample-size calculations depend on assumptions about the effect, variability or event rate, significance level, allocation, and analysis method. Changing those assumptions changes the planning result. A calculation based on an observed effect can be particularly uncertain when that effect comes from a small dataset. No numerical planning result or underlying observed effect is stated in the registry record, so there is no basis for interpreting a particular required sample size or power value.

Finally, the registry lists a secondary PET-CT outcome but does not provide its analysis. The method for analyzing change, the handling of missing scans, and any adjustment for examining multiple outcomes are not reported in the registry record. General methods such as modeling repeated measurements or adjusting for multiplicity should not be presented as methods used in this trial unless the record says so. In this case, the record does not identify those procedures.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary completion outcome and a secondary outcome concerning change in standard uptake value from preoperative to postoperative PET-CT. It reports two outcome measures and no analysis records. It does not state whether additional endpoints were prespecified, how outcome priority was determined, or whether any adjustment was planned for testing more than one outcome. A multiplicity strategy is not reported in the registry record.

As a general statistical point, examining multiple outcomes or multiple analyses can increase the chance of finding an apparently notable result by chance. Prespecifying a primary outcome and describing any planned adjustment helps readers understand how to interpret results. Here, the record labels the completion count as primary and the PET-CT change as secondary, but it does not provide a statistical analysis plan or a multiplicity procedure. Since outcome analyses are not listed, there are no posted estimates or tests to interpret for either outcome.

The registry does not describe how incomplete treatment, missing follow-up, missing PET-CT scans, or other missing outcome data were handled. It also does not identify an analysis population or explain whether participants were analyzed according to treatment received, treatment started, or another rule. These details are not reported in the registry record. As a general matter, missingness can affect both the number included in an analysis and the interpretation of the results, particularly when the endpoint requires completing several stages of care. The record does not provide enough information to judge whether missing data occurred or how they might have affected any analysis.

The reason for termination and any changes to outcome definitions or analysis plans are likewise not reported in the registry record. These absences should not be filled by assuming a particular protocol or analysis approach.

11. 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.

Most frequent non-serious adverse event terms

The registry reports safety counts for the Afatinib Single Agent group. For serious adverse events, it lists 2 participants at risk and 0 affected. It lists 0 deaths. For other adverse events, it lists 2 at risk and 2 affected. These entries should be read as counts in the registry, not as a complete account of the events experienced during the trial.

The record does not give event terms for the serious adverse event category; no top serious terms are listed. It does not describe the types of other adverse events, when they occurred, how severe they were, how long they lasted, whether they led to treatment discontinuation, or whether they were judged related to afatinib. The categories therefore provide limited descriptive information rather than a detailed safety profile.

As a general statistical point, zero recorded serious events in a small study does not establish that the risk is absent. Similarly, a count of participants affected does not describe how many events each participant experienced. Interpretation also depends on follow-up completeness and event-collection procedures, which are not reported in the registry record. The recorded counts should be kept separate from claims about tolerability or causation.

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

The record establishes that ATTAIN was registered as a phase 2, single-group study of afatinib before planned surgery for NSCLC. It gives the dose schedule, the primary endpoint definition, a named secondary PET-CT outcome, and limited safety counts. It also lists enrollment as 2 and status as TERMINATED. These details describe the registered study and its recorded data fields; they do not amount to a complete results analysis.

The primary endpoint asks whether participants met a combined treatment, surgery, and postoperative-care definition. The registry record does not report the number who met that definition. Therefore, it does not show the observed rate of treatment completion or the precision of an estimate. The record also does not report the secondary PET-CT outcome analysis. The presence of an endpoint description should not be read as evidence that the endpoint was achieved or that a change was observed.

The safety entries report 0 affected for serious adverse events, 0 deaths, and 2 affected for other adverse events, with 2 at risk in each category. They do not identify the other adverse events or supply enough context to judge their clinical importance or relationship to treatment. They are descriptive counts, not proof that treatment was safe or unsafe.

Because the design is single group, the registry record cannot compare outcomes with a control group. It therefore cannot establish whether any observed outcome was caused by afatinib or how outcomes would compare under an alternative. The record does not report the reason for termination, a statistical analysis plan, or outcome analyses. Consequently, the appropriate interpretation is narrow: the study's stated aims and definitions are documented, but the posted registry entries do not establish treatment completion, comparative benefit, or a complete safety assessment.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary outcome is a composite process milestone in a preoperative setting. Completion requires not only a minimum treatment duration but also thoracotomy for the planned resection and postoperative care through 30 days. That definition makes the endpoint directly connected to the sequence of care described in the record, while also meaning that several conditions must be met for a participant to count as having completed treatment.

Such a definition raises general questions about how endpoints should be interpreted. A participant who does not meet the full definition may differ from one who does for multiple reasons, and the record does not separately report the components of the completion rule. A count of completed treatment would therefore be easier to interpret if accompanied by component-level counts and clear descriptions of the analysis population. Those results and details are not reported in the registry record.

The single-group design also illustrates the distinction between describing outcomes and estimating comparative effects. A study without a comparator can document what happened among treated participants, but it cannot directly estimate how outcomes would have differed with another strategy. The ATTAIN record makes this design explicit through its single-group model, allocation marked NA, and masking marked NONE.

Finally, the gap between a defined endpoint and an analysis result matters. A registry can identify what investigators intended to measure, while analysis records are needed to show what was observed and how uncertain the estimate is. Here, no outcome analysis records are listed. The record therefore provides useful design and endpoint context, but it cannot answer the primary clinical question with an observed completion estimate. This distinction is central to responsible interpretation of small early-phase studies.

14. 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 registry record has important trial-specific limitations for interpretation. Enrollment is listed as 2, and the study has a single-group design with no comparator. The record therefore does not support a controlled estimate of treatment effect. It also contains no outcome analysis records, so the primary completion count and the secondary PET-CT result are not available as analyses.

The primary endpoint combines treatment exposure, a specified surgical procedure, and postoperative care. The record defines the required milestones but does not provide component-level results or explain how participants who did not meet every criterion would be classified in an analysis. The timeframe is stated, but details of outcome ascertainment are not reported in the registry record.

The safety information is limited to counts. Serious adverse event terms are not listed, and the record does not describe the other adverse events, event timing, severity details, relatedness assessments, or follow-up completeness. The reason the study was terminated is not reported in the registry record, so the status alone cannot explain whether recruitment, treatment, follow-up, or analysis was affected.

Other information needed to assess the evidence is also not reported in the registry record, including detailed eligibility criteria, participant characteristics, the statistical analysis plan, missing-data handling, analysis populations, and any multiplicity approach. These limitations mean that the design and recorded counts can be described, but the results and their precision cannot be fully assessed from the registry entries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The ATTAIN Study: A Therapeutic Trial of Afatinib In the Neoadjuvant Setting — NCT02271906.
• Registry record last updated 2019-04-30; status last verified 2019-04.
• Results first posted 2019-04-30.
• 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.

18. Record Summary

NCT02271906 is the registry record for the ATTAIN Study, a phase 2, single-group trial of afatinib before surgery for NSCLC. The intervention is listed as BIBW 2992, 40 mg by mouth daily for a minimum of 14 days and until surgery. The primary outcome is the number of participants meeting a completion definition that includes treatment, thoracotomy for planned resection, and 30 days of postoperative care.

The record lists enrollment as 2, status as TERMINATED, and no analysis records. It reports serious adverse events in 0 affected participants, 0 deaths, and other adverse events in 2 affected participants. It does not give analysis results for the primary or secondary outcome, explain the reason for termination, or report a statistical analysis plan. The registry therefore documents the design, endpoint definition, and limited safety counts, but does not establish the trial's outcome.