Metformin as a Chemoprevention Agent in Non-small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Metformin as a Chemoprevention Agent in Non-small Cell Lung Cancer (NCT01717482), a randomized phase 2 study. The primary outcome is Evaluate Feasibility of Patient Randomization, Accrual, and Tissue Collection for Study Conduction.

2. Clinical Question

The study is listed as a phase 2, randomized, parallel, unmasked trial sponsored by Mayo Clinic. Its enrollment is 6. The registry record identifies the study as terminated and states that it ended because of poor accrual and funding ending. These features are central to interpreting the record: the stated primary aim was whether the study processes could be carried out, while the available record does not report a primary outcome result or an estimate comparing treatment groups.

3. Trial Design

The registry record describes a randomized, parallel-group, unmasked phase 2 study. Randomization means assignment to study groups was intended to occur by chance; a parallel design means the groups were followed as separate arms rather than participants crossing between study treatments. Unmasked means masking is listed as none. The record does not explain the randomization procedure, concealment of allocation, or whether any outcome assessment was masked.

The arm descriptions identify Metformin, at 850mg twice a day, and Observation, described as standard of care observation. In the intervention list, the registry also includes Placebo Comparator. The difference in labels is worth noting: the record does not provide a fuller explanation of how the placebo entry relates to the Observation arm description. The study summary describes the intended comparison as metformin with standard of care against standard of care alone.

The planned primary assessment was feasibility of patient randomization, accrual, and tissue collection after resection of stage IA-IIIA lung squamous cell cancer. Its listed timeframe is 2 years. The study began in 2012-10 and has a primary completion date of 2019-05-22; the record does not explain the relationship between that date and the stated timeframe. Enrollment is 6. The status is terminated, and the primary outcome description says the study terminated because of poor accrual and funding ended.

The design should therefore be read as a pilot feasibility study, not as a completed efficacy comparison. The registry record lists four outcome measures and zero analyses. It does not report a detailed statistical analysis plan, allocation ratio, analysis populations, or an account of recruitment over time. A phase label alone does not fill in these missing details or establish that efficacy was demonstrated.

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

Analysis population for the primary outcome, as defined in the registry: Study terminated due to poor accrual and funding ended

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 Evaluate Feasibility of Patient Randomization, Accrual, and Tissue Collection for Study Conduction, measured over 2 years.

The primary endpoint addresses whether it was feasible to conduct a larger or more complete study process: could patients be randomized, could accrual proceed, and could tissue be collected? The record describes assessing reasons patients declined randomization, tracking accrual, and tracking tissue collection and reasons tissue was not collected. The stated timeframe is 2 years.

Feasibility is a process outcome rather than a measure of whether metformin changes cancer outcomes. It is used in pilot research to identify practical barriers to recruitment, assignment, and specimen collection. Such information can help characterize whether study procedures are workable and where difficulties arise. It does not, by itself, establish an effect on disease or any other clinical outcome.

The registry record does not present a single numerical primary endpoint result. It identifies the study as terminated because of poor accrual and funding ended. It also notes that the primary outcome has several categories or time points and was not reduced to one comparison. No figures for recruitment progress, reasons for declining randomization, tissue collection, or reasons for missing tissue are reported in the registry record. As a result, the endpoint’s intended scope is clear, but its component results and precision cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

In general, randomization assigns participants to study groups using chance. When properly implemented, it is intended to reduce systematic differences between groups at the point of assignment. It does not guarantee that groups will be alike in every respect, particularly in a small study, and it cannot compensate for incomplete outcome reporting. The registry record identifies the study as randomized but does not describe the sequence-generation method, allocation concealment, or how assignment was carried out.

The record describes a parallel design, with Metformin and Observation arms, and lists masking as none. In general, lack of masking means participants or study personnel may know the assigned group, depending on the procedures used. That knowledge can affect treatment delivery, reporting, or assessment in some settings. The registry record does not specify which people knew assignments or whether outcome assessors were masked, so those details cannot be evaluated.

What kind of outcome was primary?

The primary outcome was feasibility of randomization, accrual, and tissue collection, rather than a single clinical treatment effect. In general, feasibility outcomes can include process counts and reasons for success or difficulty. They help describe whether recruitment and study procedures can be carried out. Different components may have different denominators or time points, so collapsing them into one summary can obscure what worked and what did not. The registry record says the primary outcome includes several categories or time points and was not reduced to one comparison.

The record describes tracking reasons patients declined randomization, accrual numbers, whether tissue was collected, and reasons tissue was not collected. It does not report the component observations or a single estimate for these measures. The stated timeframe is 2 years, but no details are given about when each component was assessed or how incomplete observations were handled.

How should the safety counts be understood?

The adverse-event information gives group-level counts for participants at risk and affected. In general, a count is a descriptive summary; it does not express the uncertainty around an event frequency or establish that a difference between groups is meaningful. Small group sizes can make such summaries especially unstable. The record lists serious adverse events separately from other adverse events and also reports deaths. These categories should not be combined without a prespecified definition and supporting information. No serious adverse event terms are listed in the record.

General comparisons of adverse-event frequencies require attention to the definition of an event, the period during which participants were observed, and whether participants could have more than one event. The registry record does not report those details. The reported counts therefore describe what is listed, but do not support a broader safety comparison or causal conclusion.

What do planning calculations mean?

In general, a sample-size calculation translates a chosen target effect and statistical assumptions into a planning quantity. It is not an observed result and is not the same as observed power. The registry record describes planning illustrations based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It distinguishes participant counts per arm for non-time-to-event outcomes from total event counts for time-to-event calculations. These are described as illustrations, not as the study’s own design.

Those assumptions do not establish that the trial was planned with those targets or that its analyses used those methods. The record does not provide a study-specific sample-size justification, a target effect for the original design, or a detailed inferential analysis plan. No planning estimate should be interpreted as evidence that the study had sufficient precision or as proof that a treatment effect was present.

What can an uncertainty interval tell a reader?

In general, a confidence interval describes the range of values compatible with an estimate under a specified statistical procedure. A narrower interval indicates greater precision, while a wider interval indicates greater uncertainty. An interval does not remove concerns about bias, missing outcomes, or the suitability of the underlying analysis. No primary estimate or confidence interval is reported in the registry record, so its precision cannot be assessed in that way.

General statistical testing also depends on a defined outcome, analysis population, model, and assumptions. For counts or rates, the choice of method may depend on the event structure and observation period. When variation exceeds what a simple model expects, over-dispersion can make standard errors too small if it is ignored; methods that account for the extra variability may be needed. This is a general point, not a description of an analysis reported for this study. The registry record lists zero analyses and does not identify a model or test for the primary outcome.

For this study, the primary statistical interpretation is constrained by the reporting: the design and outcome purpose are described, but no primary estimate is presented. Descriptive safety counts remain descriptive, and the record’s termination reason should be interpreted as a study-conduct outcome rather than a treatment-effect estimate.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures, including the primary feasibility outcome and secondary outcomes concerning metformin sensitivity in induced pluripotent stem cells (iPS) and participants with adverse events as a measure of safety. It does not provide results for these secondary outcomes in the information recorded. The record lists zero analyses. It also indicates that the primary outcome has several categories or time points and was not reduced to one comparison.

Multiplicity arises in general when several outcomes, time points, or comparisons are examined. Testing many hypotheses can increase the chance of finding a nominally unusual result by chance. Appropriate interpretation depends on whether hypotheses were prespecified and whether an adjustment or hierarchy was planned. A multiplicity strategy is not reported in the registry record. Because no primary comparison or analysis details are reported, the effect of multiplicity on any inference cannot be assessed.

Missing-data methods and the treatment of incomplete observations are not reported in the registry record. This matters for a feasibility endpoint that explicitly tracks tissue not collected and reasons for non-collection: missing tissue may be part of the outcome being described, but the record does not give the component results or explain how incomplete records were handled. The analysis populations, including whether analyses would use all randomized participants or another defined group, are also not reported. The record therefore does not support reconstruction of an analysis set or an assessment of attrition-related bias.

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 record lists serious adverse events and other adverse events separately. For Metformin, 4 participants are listed as at risk for serious adverse events, with 0 affected; 4 are listed as at risk for other adverse events, with 1 affected. For Observation, 2 are listed as at risk for serious adverse events, with 0 affected; 2 are listed as at risk for other adverse events, with 0 affected. Deaths are listed as 0 in both groups. No serious adverse event terms are listed.

These are reported counts, not adjusted comparisons or evidence that the groups have equivalent safety. The record does not give details about event definitions, observation duration, recurrence, severity among other events, or how the participants at risk were determined. With limited enrollment, counts can be highly uncertain, and a zero count does not establish that an event cannot occur. The registry record does not report a statistical safety analysis. The counts should therefore be read as the limited safety information recorded, without converting them into a treatment-effect or risk comparison.

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

This record documents a randomized, unmasked phase 2 pilot study designed to assess whether randomization, accrual, and tissue collection could be carried out for a metformin-versus-observation study after resection of stage IA-IIIA lung squamous cell cancer. It also documents termination, with poor accrual and funding ending identified as the reason. The enrollment is 6. These details show why the feasibility objective is central to interpreting the study.

The record does not report a numerical primary outcome result, a primary comparison between groups, or results for the listed secondary outcomes. It therefore does not establish whether metformin changed a clinical outcome or whether the treatment groups differed in efficacy. It also does not provide a basis for concluding that there was no effect. Without an estimate and its uncertainty, the treatment question remains unanswered by the information in this registry record.

The limited adverse-event counts describe recorded events, but they do not determine comparative safety. In particular, zero serious adverse events or deaths in the listed groups is not proof that such events are impossible or that the treatments have the same safety profile. Interpretation is also constrained by absent details about event definitions, observation time, analysis populations, missing data, and statistical methods.

In general, a feasibility study can inform the practicality of recruitment and procedures even when it cannot answer an efficacy question. In this case, the stated termination reason points to difficulty with accrual and funding, but the record does not provide the detailed accrual trajectory or process outcomes needed to quantify those challenges. The most defensible reading is therefore descriptive: the registry records the study’s intended feasibility purpose, its terminated status, and a small set of safety counts, while leaving the primary and secondary outcome results unreported.

13. Why This Trial Matters Statistically

This study is statistically notable because its primary purpose was feasibility, not a direct test of clinical benefit. Pilot studies often focus on whether recruitment, randomization, and data or specimen collection are workable. These questions are distinct from whether an intervention improves a health outcome. Keeping that distinction clear prevents a feasibility record from being overinterpreted as an efficacy trial result.

The study’s termination for poor accrual and funding ending illustrates how trial conduct can limit what statistical conclusions are possible. Enrollment is 6, and the registry record does not report a primary endpoint estimate. Randomization can support fair comparisons when enough outcome information is collected, but random assignment alone cannot produce an interpretable treatment effect if results are not reported or the study ends before the planned work is completed.

The primary endpoint also spans multiple process components: reasons for declining randomization, accrual, tissue collection, and reasons tissue was not collected. Each component can answer a different operational question. The record’s note that the outcome was not reduced to one comparison is important because a single summary could conceal meaningful differences among those processes. At the same time, without component results, readers cannot identify where the main obstacle occurred beyond the reported poor accrual.

Finally, the limited safety counts demonstrate the distinction between descriptive data and inferential evidence. Counts can inform a record of observed events, but they do not, on their own, establish a comparative safety conclusion. This study therefore matters statistically as an example of why endpoint purpose, study status, and completeness of outcome reporting must be considered before interpreting a clinical trial record.

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 main limitation is that the registry record does not report a numerical result for the primary feasibility outcome. The record says the outcome includes several categories or time points and was not reduced to one comparison. Although the study’s purpose and the process measures are described, the results for accrual, randomization decisions, and tissue collection are not reported in the registry record.

Enrollment is 6, and the study is listed as terminated because of poor accrual and funding ended. This limits the amount of information available for describing feasibility and prevents a meaningful treatment-group comparison from being interpreted. The record does not provide a recruitment timeline, details of eligibility or screening, or counts of people who declined randomization.

The intervention descriptions also differ in wording: the intervention list includes Placebo Comparator, while the arm descriptions name Metformin and Observation, with standard of care observation. The summary frames the comparison as metformin with standard of care versus standard care alone, but the record does not explain the relationship between the placebo listing and the observation arm in further detail.

Other limitations include the absence of reported secondary outcome results, zero listed analyses, and no reported analysis populations, missing-data methods, or detailed statistical analysis plan. Safety information is limited to counts, without further event definitions, follow-up details, or serious-event terms. The registry record also does not explain how the 2 years listed as the primary outcome timeframe relates to the primary completion date of 2019-05-22. These omissions restrict both reproducibility and interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Metformin as a Chemoprevention Agent in Non-small Cell Lung Cancer — NCT01717482.
• Registry record last updated 2020-03-10; status last verified 2020-03.
• Results first posted 2019-06-19.
• 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

NCT01717482 is a Mayo Clinic phase 2 randomized, parallel, unmasked study of metformin as a chemoprevention agent in non-small-cell lung cancer. The Metformin arm is described as 850mg twice a day; the Observation arm is described as standard of care observation. The registry record also lists Placebo Comparator among the interventions.

The primary aim was feasibility of randomization, accrual, and tissue collection after resection of stage IA-IIIA lung squamous cell cancer. Enrollment is 6. The study began in 2012-10, has a primary completion date of 2019-05-22, and is listed as terminated because of poor accrual and funding ended. The record lists four outcome measures and zero analyses, but does not report a primary outcome comparison or secondary outcome results. Safety counts are reported descriptively; they do not support a comparative treatment conclusion.