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 Methods Project 4: Clinical Trial (NCT01867242), a randomized na study. The primary outcome is Smoke-free Days.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01867242 |
| Phase | NA |
| Condition | Smoker |
| Allocation | Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 150 |
| Arms in the primary outcome | 3 |
| Lead sponsor | University of Minnesota |
| Results posted | Yes |
2. Clinical Question
The trial concerns cigarette smokers who entered a Camel Snus sampling phase and were interested in continuing. The registry summary describes a 2 week baseline assessment followed by randomization to experimental conditions for 8 weeks. The primary question is descriptive and comparative: how many days without cigarette smoking were reported during the intervention in each group?
Population
Cigarette smokers eligible for the sampling phase who continued into the study. The registry lists the condition as Smoker. It does not give further eligibility details or identify a more specific primary analysis population.
Intervention
Participants assigned to complete substitution were instructed to use snus in place of cigarettes. Participants in the partial-substitution group were told they could use snus and cigarettes as they liked.
Comparator
The usual-brand cigarette group continued smoking its usual brand during the intervention. The arm description says participants would be offered Camel Snus after 8 weeks and could choose partial or complete substitution.
Primary question
How did the number of days with no cigarette smoking compare across the three assigned conditions during the 8-week intervention? The posted endpoint is the number of days subjects smoked no cigarettes, summarized by group medians and full ranges.
The record also identifies measures of tobacco use patterns, subjective product responses, and nicotine and toxicant exposure in its study summary. Three secondary outcomes are named: CEMA, Total Nicotine Exposure, and Urinary Total NNAL. The posted information does not establish whether the primary comparison was intended to test a particular superiority or noninferiority hypothesis.
3. Trial Design
The registry describes a randomized study with no masking and a single-group model label. At the same time, it lists three study groups: Complete Substitution, Partial Substitution (Snus and Cigarettes), and Usual Brand Cigarette. The registry record does not explain the single-group model label alongside those three listed conditions, nor does it describe the randomization procedure or allocation ratio.
The study summary describes a sequence in which eligible smokers entered a Camel Snus sampling phase. Those interested in continuing then underwent a 2 week baseline assessment and were randomized to one of three experimental conditions for 8 weeks. The record lists planned enrollment of 150. The study status is completed; the recorded start is 2013-07 and primary completion is 2017-02.
The complete-substitution arm was instructed to use snus instead of cigarettes. The partial-substitution arm could use snus and cigarettes how ever they liked, as worded in the arm description. The usual-brand control continued smoking usual-brand cigarettes during the intervention; after 8 weeks, that group was to be offered Camel Snus and instructed in partial or complete substitution according to the participant’s choice. This post-intervention offer is part of the arm description, not part of the primary endpoint period.
The posted primary results include 64 participants in the complete-substitution group, 60 in the partial-substitution group, and 26 in the usual-brand group. These are the group sizes attached to the posted endpoint values; the registry does not explain any difference between these analyzed group sizes and the planned enrollment. The record does not report masking, and it does not describe procedures for maintaining adherence to assigned product use.
The registry identifies four outcome measures in total and lists three secondary outcomes, but it does not provide posted analyses for those secondary outcomes in the information summarized by the endpoint results. Details such as a protocol-defined analysis population, the timing of assessments within the intervention, and a statistical analysis plan are not reported in the registry record.
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: After 1 week, participants returned to the clinic with snus tins and unused snus pouches. Tobacco use over the past week was assessed and participants completed self-report questionnaires. Participants who used at least seven snus pouches (based on potential use of one pouch per day) and continued to smoke were eligible to enter the clinical trial. These criteria were withheld from participants to ensure an unbiased willingness to use snus.
Overall Study
| Stage | Complete Substitution | Partial Substitution (Snus and Cigarettes) | Usual Brand Cigarette |
|---|---|---|---|
| STARTED | 64 | 60 | 26 |
| COMPLETED | 40 | 44 | 18 |
| NOT COMPLETED | 24 | 16 | 8 |
Reasons for not completing this period:
| Reason | Complete Substitution | Partial Substitution (Snus and Cigarettes) | Usual Brand Cigarette |
|---|---|---|---|
| Lost to follow-up, personal reasons | 24 | 16 | 8 |
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 | Complete Substitution | Partial Substitution (Snus and Cigarettes) | Usual Brand Cigarette | Total |
|---|---|---|---|---|---|
| Participants analysed | 64 | 60 | 26 | 150 | |
| Age, Continuous | years | 42.5 (18 to 83) | 42.0 (18 to 64) | 47.0 (23 to 68) | 43.5 (18 to 83) |
| Sex: Female, Male: Female | Participants | 28 | 24 | 13 | 65 |
| Sex: Female, Male: Male | Participants | 36 | 36 | 13 | 85 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 16 | 16 | 11 | 43 |
| Race (NIH/OMB): White | Participants | 44 | 43 | 15 | 102 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 4 | 1 | 0 | 5 |
| Region of Enrollment: United States | participants | 64 | 60 | 26 | 150 |
| Mean cigarettes per day (CPD) | Cigarettes Per Day | 14.0 (4.3 to 34.4) | 11.7 (6.0 to 39.9) | 12.1 (5.6 to 31.5) | 12.3 (4.3 to 39.9) |
| Fagerstrom Test for Nicotine Dependence (FTND) | units on a scale | 3.0 (2 to 6) | 3.0 (0 to 7) | 3.0 (1 to 6) | 3.0 (0 to 7) |
| Total Nicotine Equivalents (TNE) | nmol/mg | 58.3 (18.5 to 383.1) | 55.9 (0.04 to 307.3) | 65.7 (5.4 to 152.4) | 59.1 (0.04 to 383.1) |
6. Primary Endpoint
The registry lists the primary outcome as Smoke-free Days, measured over 8 weeks (56 (+/-5) days).
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | days |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is Smoke-free Days, measured in days over the 8-week intervention, specified as 56 (+/-5) days. It is defined as the number of days subjects smoked no cigarettes during the intervention. This is a count of days without cigarette smoking, not a measure of the amount smoked on days when participants did smoke.
A day-based endpoint can describe whether participants experienced any cigarette-free days during the study period and how such days were distributed across participants. The median gives the middle of the observed group values, while the full range shows the lowest and highest reported values. These summaries are useful for a count outcome whose values may be concentrated at zero or distributed unevenly. They do not, by themselves, describe the complete shape of the distribution or quantify uncertainty around a group comparison.
The record’s endpoint metadata classifies the outcome as a median with full-range dispersion. Although a separate metadata label refers to a time-to-event kind, the endpoint description itself defines a number of days without cigarette smoking. No event definition, event-time analysis, or sponsor-reported hazard ratio for this primary result is included in the posted information. The record does not explain this metadata distinction.
In the complete-substitution group, the median was 14.5 days, with a full range from 0.0 to 61.0. In each of the other two groups, the median was 0.0 days and the full range was 0.0 to 0.0. These summaries describe the posted endpoint values; they do not establish the reason for the observed pattern or the precision of a contrast between groups.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The endpoint summaries differ across the groups. The complete-substitution group had a median of 14.5 smoke-free days, and its full range extended from 0.0 to 61.0 days. The partial-substitution group and the usual-brand cigarette group each had a median of 0.0 days and a full range of 0.0 to 0.0. Thus, the posted summaries show that the complete-substitution group included variation in reported smoke-free days, while the posted values in the other two groups were all at zero.
A median describes a central position, not an average and not the experience of every participant. In a group with a median of 0.0, it would be inappropriate to conclude from the median alone that every participant had an identical experience. Here, the accompanying full range also runs from 0.0 to 0.0 in both groups, which indicates that the observed endpoint values represented in those summaries were all zero. The registry does not describe how missing or unavailable endpoint values were handled, so the summaries should be interpreted as posted rather than as proof that every randomized participant contributed an observed value.
The group sizes associated with the results are 64 for complete substitution, 60 for partial substitution, and 26 for usual-brand cigarette use. The group sizes are unequal, and the record does not explain the reasons for those sizes or give a participant flow account. The endpoint summaries therefore do not reveal whether differences in completion, adherence, or other factors affected which data were included.
No inferential analysis for a comparison of these medians is posted. The registry record does not report a p-value, confidence interval, adjusted estimate, or effect estimate for the primary endpoint. The data therefore support a description of the reported group summaries, but not a claim about statistical significance or the precision of a group contrast. The absence of a posted inferential result also means that the apparent separation in these summaries cannot be translated into a formal estimate of uncertainty using the registry information.
The record lists three secondary outcomes: CEMA (2-cyanoethylmercapturic Acid), Total Nicotine Exposure, and Urinary Total NNAL. Their names indicate measures beyond the smoke-free-day endpoint, but no corresponding results or analyses are reported in the information available for interpretation. The registry summary also describes assessment of tobacco use patterns, subjective responses, and nicotine and toxicant exposure without posting results for those measures in this endpoint record.
These results should be read as an account of the registered endpoint values, not as a conclusion about clinical benefit or harm. The registry describes assigned conditions and observed summaries but does not establish why participants had the recorded values, whether the conditions were followed as intended, or whether the result would generalize beyond this study population.
9. Statistical Methods Explained
The reported primary summaries are medians and full ranges. These are descriptive statistics: they characterize the observed endpoint values within each group without, by themselves, testing whether the groups differ beyond what could arise from sampling variation. The registry record does not report a statistical test or an inferential estimate for the primary endpoint.
What does a median communicate?
The median is the central ordered observation, or the central pair of observations when the number of observations is even. It is often useful when values are skewed or concentrated at a boundary because it is less affected by unusually large values than the arithmetic mean. For Smoke-free Days, a median of 0.0 indicates that the central position of the group’s observed values is at zero. It does not, without additional information, describe all values in that group. The full range adds information about the endpoints of the observed values but does not show how frequently values occurred between those endpoints.
For the complete-substitution group, the reported median is 14.5 and the full range is 0.0 to 61.0. For the partial-substitution and usual-brand cigarette groups, the median and both range endpoints are 0.0. The values in the complete-substitution group include a maximum beyond the stated 8-week timeframe of 56 (+/-5) days. The registry does not explain the relationship between that maximum and the endpoint timeframe, so the value is reported as recorded rather than reconciled or reinterpreted.
Why does the distribution matter?
Count outcomes can be skewed, and a substantial concentration at zero can create a distribution that is not well represented by a normal, symmetric model. In general, over-dispersion means that observed variability is greater than a model’s assumptions allow; ignoring it can make standard errors and resulting uncertainty estimates unreliable. This is a general statistical consideration, not a statement that a particular model was used or that over-dispersion was demonstrated in this trial. The registry does not report a distributional assessment or model for the primary endpoint.
The full range is not a confidence interval. A range reports the lowest and highest observed values, whereas a confidence interval is an inferential interval intended to express uncertainty around an estimated quantity under specified assumptions. The record provides no confidence interval for the median or for a difference between groups. The endpoint summaries also do not indicate whether any adjusted analysis was planned or conducted.
What can a group comparison establish?
A formal comparison would need to define the target contrast and use a method appropriate to the endpoint and the study design. Possible methods for a count outcome depend on its distribution, the handling of zeros, and whether the estimand concerns a group median, a mean count, a rate, or another feature. These approaches answer different questions. No such method is identified for the primary result in the registry record, so no particular model or test should be attributed to the trial.
Random assignment can support a causal comparison when the analysis follows a suitable plan and accounts appropriately for the randomized participants and missing outcomes. The registry identifies the study as randomized, but it does not state the analysis population, the handling of departures from assigned use, or how missing outcome values were treated. Without these details, the group summaries alone do not establish the effect of assignment under a clearly specified estimand.
How should uncertainty be read?
Uncertainty concerns how much the estimated result might vary across repeated samples under an assumed design and model. A confidence interval communicates a range of values compatible with the data and assumptions; a p-value addresses how unusual the data would be under a specified null hypothesis and model. Neither quantity is posted for the primary endpoint comparison. A small or large difference between descriptive summaries cannot substitute for these missing inferential results, and the registry does not give enough information to reconstruct them reliably.
The record labels the endpoint as a median-time type and notes that time-to-event tables use sponsor-reported hazard ratios. However, no sponsor-reported hazard ratio is listed for this endpoint. The endpoint description is a count of days smoked no cigarettes, and the posted results are medians and full ranges. A hazard ratio should not be inferred from these summaries; time-to-event methods require event and censoring information that is not reported.
What do planning calculations mean?
Planning calculations based on an observed effect are illustrations of the number of participants that could be needed under stated assumptions. They are not an account of the study’s original design justification, and they are not observed power. The record’s general assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The record does not report that these were the trial’s own planning assumptions or justify the trial’s enrollment. In particular, the study lists three groups, while the stated illustration assumptions concern two arms; the illustration should not be mistaken for the registered three-group design.
Because the primary endpoint comparison has no posted inferential analysis, there is no sponsor-reported hazard ratio to interpret and no basis in the registry record for estimating uncertainty around a treatment contrast. The descriptive values remain informative as summaries of the posted data, but they answer a more limited question than a prespecified inferential analysis would.
10. Multiplicity, Missing Data and Analysis Populations
The registry names three secondary outcomes: CEMA (2-cyanoethylmercapturic Acid), Total Nicotine Exposure, and Urinary Total NNAL. It does not report results for these outcomes in the posted endpoint information. A broader study summary also mentions tobacco use patterns, subjective responses to product, and nicotine and toxicant exposure. The registry record does not explain how these measures relate to the listed outcome measures or identify a hierarchy among them.
When a study evaluates multiple outcomes or makes multiple comparisons, the chance of at least one apparently noteworthy result can increase. Statistical plans may address this through a prespecified primary outcome, a hierarchy of tests, or an adjustment for multiple testing. The registry record does not report a multiplicity strategy, so it is not possible to determine whether any adjustment was planned or applied. This is especially relevant when interpreting secondary results, if they are reported elsewhere, because their role and inferential status are not defined in this record.
The record gives no posted analyses for the primary endpoint comparison and no analysis counts. It also does not report an analysis population, such as whether results were based on all randomized participants or only those with endpoint data. Although randomized group sizes are attached to the endpoint summaries, missing-data counts, reasons for missingness, and imputation or other missing-data procedures are not reported in the registry record.
Interim analyses, stopping boundaries, and a statistical analysis plan are also not reported in the registry record. This does not establish that such procedures were or were not used; it means the posted information does not describe them. Without a prespecified analysis description, readers cannot assess whether the posted summaries follow an intended plan or how missing data and multiple outcomes were meant to be handled.
11. 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 |
|---|---|---|---|
| Complete Substitution | 1 | 64 | 1.6% |
| Partial Substitution (Snus and Cigarettes) | 0 | 60 | 0.0% |
| Usual Brand Cigarette | 0 | 26 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Complete Substitution | 0 of 64 |
| Partial Substitution (Snus and Cigarettes) | 0 of 60 |
| Usual Brand Cigarette | 0 of 26 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Complete Substitution | 5 of 64 |
| Partial Substitution (Snus and Cigarettes) | 1 of 60 |
| Usual Brand Cigarette | 0 of 26 |
Most frequent serious adverse event terms
| Event term | Organ system | Complete Substitution | Partial Substitution (Snus and Cigarettes) | Usual Brand Cigarette |
|---|---|---|---|---|
| Hospitalization | Injury, poisoning and procedural complications | 1 of 64 | n/a of 60 | n/a of 26 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Complete Substitution | Partial Substitution (Snus and Cigarettes) | Usual Brand Cigarette |
|---|---|---|---|---|
| Gum sensitivity | Gastrointestinal disorders | 5 of 64 | 1 of 60 | 0 of 26 |
| Hearburn/reflux | Gastrointestinal disorders | 4 of 64 | 1 of 60 | 0 of 26 |
| Nausea | Gastrointestinal disorders | 4 of 64 | 1 of 60 | 0 of 26 |
| Irritability | Psychiatric disorders | 3 of 64 | 0 of 60 | 0 of 26 |
Serious events with the highest arm-level rate: hospitalization (1.6%).
The registry reports serious adverse events and other adverse events by group, alongside the number at risk in each group. In the complete-substitution group, 1 of 64 participants is listed with a serious adverse event and 5 of 64 with other adverse events. In the partial-substitution group, the corresponding counts are 0 of 60 and 1 of 60. In the usual-brand cigarette group, both counts are 0 of 26. No deaths are reported in any group.
The record lists Hospitalization at 1.6% among the top serious-event terms. The posted information does not give enough detail to establish the event’s timing, clinical context, or relationship to study product use. A listed event is not, by itself, evidence that the assigned condition caused it. Conversely, the absence of reported events in a group does not establish that no risk exists.
These counts are descriptive. The registry does not provide an inferential comparison of adverse-event rates, nor does it report event-level narratives or a method for assessing causality. Group sizes differ, and the record does not describe how adverse-event follow-up was conducted or how missing safety information was handled. The figures should therefore be read as the events recorded in this registry entry, not as a complete safety assessment or a basis for comparing risks.
12. What the Result Does, and Does Not, Mean
The primary result describes a difference in the posted smoke-free-day summaries across the assigned groups. The complete-substitution group had a median of 14.5 days and a full range from 0.0 to 61.0. The partial-substitution and usual-brand cigarette groups each had a median and full range of 0.0. These are the central values and observed ranges reported by the registry, not estimates accompanied by a measure of statistical uncertainty.
The result does not show how precise a contrast between groups is. No confidence interval, p-value, or adjusted comparison for the primary endpoint is reported. It is therefore not possible to use the registry entry to determine whether the observed difference is statistically distinguishable from sampling variation under a specified model. Nor does the record establish that the differences arose solely from assigned product use.
The endpoint has a specific interpretation: days on which participants smoked no cigarettes during the intervention. It does not quantify cigarette consumption on other days, nor does it establish patterns of snus use. The study summary says tobacco use patterns and subjective responses were assessed, and it identifies exposure outcomes, but the corresponding results are not reported in the information available for this interpretation.
The registry record also does not supply a complete account of participant flow, adherence, missing endpoint values, or the analysis population. Those details matter for understanding how closely the posted groups represent all participants who were randomized and how the summaries relate to assignment. The result should not be expanded beyond the endpoint values and study conditions described in the record.
For these reasons, the posted summaries are best treated as descriptive evidence about the observed Smoke-free Days values in this trial. They do not, on their own, establish a clinical benefit, a lack of benefit, or a comparative safety conclusion. They also do not establish how the findings would apply to smokers outside the study or to tobacco-use conditions not included in the registered groups.
13. Why This Trial Matters Statistically
This trial illustrates why an endpoint’s form and its summary statistics both matter. Smoke-free Days is a count of days without cigarette smoking, and the posted results use medians and full ranges. Those summaries communicate a central value and the observed extremes, but they cannot show the distribution’s detailed shape or the uncertainty around a contrast. In this record, the summaries include values at zero in all groups and a wider range in the complete-substitution group, making the distinction between descriptive results and formal inference particularly important.
The record also shows why clarity about design and analysis is essential. It describes randomization and lists three conditions, yet labels the model single group. The registry does not explain that discrepancy. It provides group sizes and outcome summaries, but does not report a test, confidence interval, missing-data approach, or analysis population. Without those elements, readers can describe the values but cannot evaluate a prespecified inferential conclusion from the entry.
There is also a useful distinction between the study’s own design and planning illustrations based on an observed effect. Such calculations depend on assumptions and do not establish that the original enrollment was chosen to meet them. They are not observed power. The registry does not report the trial’s sample-size justification, so that rationale cannot be assessed from this record.
More broadly, the study names secondary measures relating to nicotine and toxicant exposure, but their results and multiplicity handling are not reported in the endpoint information. The example highlights how an outcome can be understandable at the descriptive level while important statistical questions—about estimation, uncertainty, missing data, and the analysis plan—remain unresolved in the registry 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 registry provides limited detail for interpreting the primary endpoint beyond its definition, timeframe, group summaries, and group sizes. It does not describe the distribution of participant-level values, report a confidence interval, or give an inferential comparison. The full ranges convey only the observed endpoints of the values, and the record does not clarify how the maximum of 61.0 relates to the stated timeframe of 56 (+/-5) days.
The design information is also incomplete. Randomized allocation is listed, but the record does not explain the randomization sequence, concealment, allocation ratio, or the reason for the single-group model label despite the three listed conditions. Masking is listed as none. The record does not report adherence measures, participant flow, or whether the posted endpoint summaries include all randomized participants or a subset with available data.
Missing outcome data and their handling are not described. The registry also does not report an analysis plan, multiplicity approach, interim analyses, stopping rules, or the sample-size justification. These omissions limit assessment of how the reported endpoint was selected and analyzed, whether all planned analyses are represented, and how robust the group summaries are to missingness or analytic choices.
The adverse-event record is limited to group counts and a listed serious-event term. It does not provide clinical narratives, event timing, relatedness assessments, or statistical comparisons. The secondary outcomes are named, but corresponding results are not included in the endpoint information. As a result, the record supports a narrow description of the posted primary and safety summaries rather than a comprehensive evaluation of the study’s outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Methods Project 4: Clinical Trial — NCT01867242.
- Registry record last updated 2023-05-03; status last verified 2023-04.
- Results first posted 2023-04-25.
- 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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18. Record Summary
NCT01867242 is a completed randomized study listed with no masking and a single-group model label. Its study summary describes smokers entering a Camel Snus sampling phase, followed by a 2 week baseline assessment and randomization to one of three conditions for 8 weeks. The recorded start is 2013-07, primary completion is 2017-02, and planned enrollment is 150.
The primary endpoint, Smoke-free Days, counts days with no cigarette smoking during the intervention and is summarized by medians and full ranges. The complete-substitution group had a median of 14.5 days, with a range of 0.0 to 61.0; the other two groups each had a median and range of 0.0. No inferential comparison is posted. The record names three secondary outcomes but does not report their results in the endpoint information.
Safety summaries list 1 serious adverse event in the complete-substitution group and none in the other groups; no deaths are reported. The registry does not describe the analysis population, missing-data procedures, multiplicity strategy, or sample-size justification.