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 Exploratory Study of ART-123 for the Prevention of Cancer Treatment Related Symptoms in Patients With Postoperative Stage II / III Colon Cancer (NCT02792842), a randomized phase 2 study. The primary outcome is The Cumulative Rates of Participants With NCI-CTCAE Grade 2 or Higher Peripheral Sensory Neuropathy: Up to End of Study Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02792842 |
| Phase | Phase 2 |
| Condition | Postoperative Stage II/III Colon Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 79 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Asahi Kasei Therapeutics Corporation |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with postoperative stage II/III colon cancer. The registry describes the neuropathy analysis population as participants who were randomly assigned, received at least one dose of study drug and oxaliplatin, and had at least one FACT/GOG-Ntx-12 or NCI-CTCAE evaluation after oxaliplatin administration. The registry record does not report further eligibility details in the outcome description.
Intervention
Two ART-123 schedules were studied: ART-123 (3-day ART) and ART-123 (1-day ART). The intervention names identify the schedules, but further administration details are not reported in the registry record.
Comparator
The comparator was placebo. The registry describes the study as randomized, placebo-controlled, double-blind, and parallel-group.
Primary question
The study evaluated whether the ART-123 schedules were associated with different cumulative counts of participants experiencing NCI-CTCAE grade 2 or higher peripheral sensory neuropathy through the end of study treatment. No primary endpoint was specified because the study was exploratory. The displayed endpoint is therefore a key outcome, but the registry does not identify it as a prespecified primary endpoint.
3. Trial Design
This was a phase 2, multicenter, randomized, placebo-controlled, double-blind study with a parallel-group design. It evaluated ART-123 in patients with postoperative stage II/III colon cancer. The three intervention groups were ART-123 (3-day ART), ART-123 (1-day ART), and placebo. The registry lists 24 participants for the 3-day ART group, 27 for the 1-day ART group, and 28 for placebo. The recorded enrollment was 79.
The study is listed as completed. Its recorded start was 2016-07, and its primary completion was 2018-02. The sponsor was Asahi Kasei Therapeutics Corporation. The official title describes the study as a phase 2 clinical study investigating the efficacy and safety of ART-123, while the brief summary describes its purpose as evaluating prevention of cancer-treatment-related symptoms.
Randomization and double masking can help reduce systematic differences in treatment assignment and outcome assessment. These are general design considerations; the registry record does not report the randomization procedure, allocation concealment details, or the specific masking arrangements. It also does not report the planned allocation ratio, the original sample-size rationale, or further details of treatment administration beyond the intervention names.
The outcome description defines an analysis population based on random assignment, receipt of study drug and oxaliplatin, and at least one post-oxaliplatin assessment. That population description is narrower than a simple statement of everyone enrolled. The registry record does not give a full account of participant flow from enrollment through the outcome analysis.
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 | ART-123 (3-day ART) | ART-123 (1-day ART) | Placebo |
|---|---|---|---|
| STARTED | 24 | 27 | 28 |
| COMPLETED | 20 | 23 | 21 |
| NOT COMPLETED | 4 | 4 | 7 |
Reasons for not completing this period:
| Reason | ART-123 (3-day ART) | ART-123 (1-day ART) | Placebo |
|---|---|---|---|
| Adverse Event | 4 | 2 | 3 |
| Withdrawal by Subject | 0 | 1 | 2 |
| Lost to Follow-up | 0 | 0 | 1 |
| Schedule delay | 0 | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: The preventive effect of ART-123 on neuropathy was analyzed in all randomly assigned participants who received at least one dose of study drug and oxaliplatin and had a FACT/GOG-Ntx-12 or NCI-CTCAE evaluation at least once after oxaliplatin administration.
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.
Population: All randomly assigned participants who received at least one dose of study drug
| Characteristic | Unit | ART-123 (3-day ART) | ART-123 (1-day ART) | Placebo | Total |
|---|---|---|---|---|---|
| Participants analysed | 24 | 27 | 28 | 79 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 11 | 9 | 10 | 30 |
| Age, Categorical: >=65 years | Participants | 13 | 18 | 18 | 49 |
| Age, Continuous | years | 66.0 (32 to 79) | 68.0 (38 to 78) | 68.0 (45 to 79) | 67.0 (32 to 79) |
| Sex: Female, Male: Female | Participants | 13 | 15 | 12 | 40 |
| Sex: Female, Male: Male | Participants | 11 | 12 | 16 | 39 |
| Race/Ethnicity, Customized: Asian | Participants | 24 | 27 | 28 | 79 |
6. Primary Endpoint
The registry lists the primary outcome as The Cumulative Rates of Participants With NCI-CTCAE Grade 2 or Higher Peripheral Sensory Neuropathy: Up to End of Study Treatment, measured over 42 days after the start of cycle 12 (each cycle is 2 weeks)..
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The recorded outcome is the cumulative count of participants who experienced NCI-CTCAE grade 2 or higher peripheral sensory neuropathy up to the end of study treatment. The stated timeframe is 42 days after the start of cycle 12; each cycle is 2 weeks. The endpoint counts whether a participant crossed the grade threshold at any point, rather than reporting the severity at a single final visit.
According to the outcome description, investigator-reported NCI-CTCAE assessments were made every day from day 1 to day 3 of each cycle, and on days 15 and 43 of cycle 12 for follow-up. Once grade 2 or higher neuropathy was observed, the participant remained classified as having reached the threshold even if later assessments returned to grade 1 or lower. Participants who discontinued or had missing evaluation data without reaching grade 2 or higher were analyzed as having no grade 2 or higher neuropathy.
A cumulative threshold outcome can capture whether the event occurred during the observation period, including an event that later improves. That is a general feature of this type of endpoint, not evidence about the course or cause of any individual participant’s symptoms. The registry explicitly states that no primary endpoint was specified because the study was exploratory.
7. Results Posted in the Registry
- ART-123 (3-day ART): 45.8% (11/24) versus 64.3% (18/28) on control; risk difference -18.5 percentage points (95% CI -45.1 to 8.2), risk ratio 0.71 (0.43–1.19); unadjusted two-proportion z-test p = 0.182.
- ART-123 (1-day ART): 40.7% (11/27) versus 64.3% (18/28) on control; risk difference -23.5 percentage points (95% CI -49.2 to 2.1), risk ratio 0.63 (0.37–1.08); unadjusted two-proportion z-test p = 0.080.
Risk difference: ART-123 (3-day ART)
95% CI: -45.1 to 8.2 percentage points
Recalculated from the posted summary statistics
8. Statistical Interpretation
The posted outcome counts were 11 participants in the ART-123 (3-day ART) group, 11 in the ART-123 (1-day ART) group, and 18 in the placebo group. The corresponding group sizes listed for this outcome were 24, 27, and 28. These are cumulative event counts under the registry’s classification rule, not counts of symptoms present only at the final assessment.
The unadjusted comparison estimates show lower observed event proportions in each ART-123 group than in placebo. The reported risk differences were negative for both comparisons: -0.184 for 3-day ART versus placebo and -0.235 for 1-day ART versus placebo. These estimates describe the observed group contrast on the risk-difference scale; they do not establish that the treatment schedules caused the difference. The unadjusted p-values were 0.182 and 0.08, respectively.
The reported intervals for both risk differences extend across zero. Thus the estimates are compatible with a range that includes no difference as well as differences favoring either group. The intervals are also broad, reflecting substantial uncertainty in these comparisons. The registry record does not report the confidence level for these intervals, so it should not be inferred from the displayed bounds.
The estimates are based on modest group sizes and an exploratory study in which no primary endpoint was specified. They should be read as descriptive comparisons rather than definitive evidence. The unadjusted p-values address each comparison as presented, but the registry record does not report whether or how multiple comparisons were handled. A p-value alone does not express the size or precision of an effect, and it does not show the probability that a treatment effect is true.
Interpretation also depends on the outcome rule. Participants without a recorded grade 2 or higher event who discontinued or had missing evaluations were classified as not having reached the threshold. This means that the posted counts do not distinguish observed absence of neuropathy from some forms of incomplete assessment. The outcome population and missing-data rule should therefore be kept in view when reading the group contrasts.
9. Statistical Methods Explained
The posted outcome is binary at the participant level: each participant is classified according to whether grade 2 or higher peripheral sensory neuropathy was observed during the defined period. The registry reports counts of participants with the event for each group, along with comparison estimates. This description concerns the posted results; details of the trial’s original statistical analysis plan are not reported in the registry record.
What does a risk difference describe?
A risk difference expresses the difference between the event proportions in two groups, on the original proportion scale. General explanation: a negative value for an ART-123-versus-placebo contrast indicates a lower observed event proportion in the ART-123 group; a value of zero represents no difference in observed proportions. The registry comparison estimates are negative for both schedules. Their reported intervals extend across zero, so they do not isolate a difference in one direction.
The registry also posts risk ratios and odds ratios for the comparisons. General explanation: a risk ratio compares event proportions as a ratio, while an odds ratio compares event odds. These measures use different scales and are not interchangeable with a risk difference. The registry record does not describe the methods used to calculate the estimates or their intervals, and the posted risk-ratio and odds-ratio bounds are not needed to interpret the risk-difference comparisons.
How should the p-values be read?
The unadjusted p-values are 0.182 for the 3-day ART comparison and 0.08 for the 1-day ART comparison. General explanation: a p-value measures how surprising data at least as inconsistent with a specified null model would be if that model were true, under the assumptions of the test. It is not the probability that the null hypothesis is true, nor a direct measure of clinical importance. The registry record does not report the test procedure or a multiplicity adjustment. These values should therefore be understood as unadjusted values as posted, not as a documented family-wise analysis.
Why do intervals matter?
General explanation: a confidence interval communicates uncertainty around an estimate. A wide interval indicates that the data are compatible with a broad range of effects, while an interval that includes the no-difference value does not rule out no difference at its stated confidence level. The posted intervals cross zero for both risk differences, and the registry does not state the confidence level. The point estimate alone therefore gives an incomplete picture of the evidence.
For binary outcomes, the amount of information depends in part on how many participants contribute outcome data and how many experience the event. Here the listed group sizes are 24, 27, and 28, and the event counts are 11, 11, and 18. These modest group sizes help explain why the comparisons are imprecise. This is a general statistical consideration, not a separately reported finding about the trial’s design.
What does the cumulative classification change?
The endpoint captures whether a participant ever reached grade 2 or higher during the assessment period. Once the threshold was reached, later improvement did not reverse the classification. This differs from comparing symptom severity at a single time point. General explanation: cumulative outcomes preserve evidence of an event that occurred earlier, but they do not describe how long it lasted or the severity pattern after it first appeared.
The outcome rule also classified participants who discontinued or had missing evaluation data without a prior grade 2 or higher event as having no such event. This rule is reported in the registry. It can affect the meaning of the count because an unobserved event is treated differently from a documented event. The registry record does not report how many participants were affected by this rule or provide a sensitivity analysis using other missing-data assumptions.
The analysis population was defined as randomly assigned participants who received at least one dose of study drug and oxaliplatin and had an eligible assessment at least once after oxaliplatin administration. This is the population specified for the preventive-effect analysis in the outcome description. It is not described as an intention-to-treat analysis, and the registry record does not report a separate intention-to-treat result.
10. Confidence Intervals and Precision
The risk-difference estimates are -0.184 for ART-123 (3-day ART) versus placebo and -0.235 for ART-123 (1-day ART) versus placebo. The registry reports an interval around each estimate. Both intervals cross zero, meaning that the posted results do not exclude no difference between the compared groups. The bounds also permit effects in either direction, so the point estimates should not be treated as precise estimates of the underlying contrast.
The reported intervals are broad in relation to the point estimates. This indicates limited precision: the data remain compatible with a range of possible group differences. The registry record does not state the confidence level associated with the intervals. It is therefore not appropriate to attach a confidence percentage to them based solely on the registry information.
Precision is constrained by the group sizes and event counts: 24 participants and 11 events for 3-day ART, 27 participants and 11 events for 1-day ART, and 28 participants and 18 events for placebo. These observed data support descriptive comparisons, but do not resolve whether the observed differences reflect a reproducible underlying effect. The unadjusted p-values, 0.182 and 0.08, do not replace the intervals as a way of understanding the range of uncertainty.
General explanation: intervals summarize statistical uncertainty under the method used to construct them; they do not account automatically for every source of uncertainty, such as choice of outcome, missing-data assumptions, or multiple comparisons. The registry record does not report the interval method or confidence level, and it does not report an adjusted interval analysis.
11. Planning a Similar Trial: Sample Size
This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.
| Effect to detect | Participants per arm, 80% power | Participants per arm, 90% power |
|---|---|---|
| 100% of the observed effect | 113 | 151 |
| 75% of the observed effect | 200 | 267 |
| 50% of the observed effect | 443 | 593 |
The sample-size figures are planning illustrations expressed as participants per arm. They are not totals across arms. For each comparison, the rows consider planning for 100%, 75%, or 50% of the observed effect. The 80% power column gives the illustrative participants per arm for a design targeting an 80% chance of detecting the specified effect under the stated assumptions; the 90% power column gives the analogous figure for a 90% target. These are planning targets, not guarantees about a future study.
The assumptions listed for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. For the comparison of 3-day ART with placebo, the participants-per-arm figures for 80% power are 113, 200, and 443 as the assumed effect moves from 100% to 75% to 50% of the observed effect; the corresponding 90% power figures are 151, 267, and 593. For the 1-day ART comparison with placebo, the respective 80% figures are 70, 124, and 274, and the respective 90% figures are 93, 165, and 367.
Smaller effects require more participants per arm under these assumptions, because a smaller group contrast is harder to distinguish from sampling variation. The curve visualizes that planning relationship. These figures are not observed power: they are sample-size illustrations derived from the observed effect, not a measure of the probability that this completed study detected a true effect. The original trial design assumptions and original sample-size justification are not reported in the registry record.
12. How the Sample Size Is Derived
Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z1−α/2 = 1.960) and the desired power (z1−β = 0.842 for 80% and 1.282 for 90%).
Formula
n is the number of participants in each arm, p0 and p1 are the control and treatment proportions, and p̄ is their average.
Worked calculation for this trial
- Control proportion p0 = 0.643; treatment proportion p1 = 0.458; average p̄ = 0.551.
- First term: z1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7035 = 1.3788.
- Second term: z1−β × √[p0(1−p0) + p1(1−p1)] = 0.842 × 0.6913 = 0.5818.
- n = (1.3788 + 0.5818)2 / (-0.1845)2 = 112.9, rounded up to 113 participants per arm for 80% power.
The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).
R code
alpha <- 0.05
z_a <- qnorm(1 - alpha / 2) # two-sided
p0 <- 0.642857142857143 # control proportion
p1 <- 0.458333333333333 # treatment proportion
n_per_arm <- function(power, frac = 1) {
q1 <- p0 + (p1 - p0) * frac # smaller effect = fraction of the observed difference
pbar <- (p0 + q1) / 2
z_b <- qnorm(power)
ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))
# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")
# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2792842)
n <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))
Output from running the code
100% of observed effect: n per arm = 113 (80% power), 151 (90% power)
75% of observed effect: n per arm = 200 (80% power), 267 (90% power)
50% of observed effect: n per arm = 443 (80% power), 593 (90% power)
power.prop.test: 112.9
Simulated power at n = 113 per arm: 0.808 (20000 replicates)The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.
13. Multiplicity, Missing Data and Analysis Populations
The registry states that no primary endpoint was specified because the study was exploratory. It lists three outcome measures and no posted secondary outcomes in the extracted record; the number of posted secondary outcomes is 0. No analyses are listed in the record. These details do not establish which outcomes or analyses were prespecified in the original protocol, or whether additional analyses were conducted elsewhere.
Two ART-123 schedules are compared with placebo for the displayed neuropathy outcome. The posted p-values are unadjusted. The registry record does not report a multiplicity strategy, such as adjustment across the schedule comparisons or across outcomes. General explanation: when several comparisons are examined, the chance of obtaining at least one apparently notable result can increase if each is assessed without accounting for the set of tests. This consideration is relevant to interpretation, but the record does not establish the exact testing family or whether any other analyses were planned.
The outcome description specifies a rule for missing data: participants who discontinued or had missing evaluation data without reaching grade 2 or higher neuropathy were analyzed as having no grade 2 or higher neuropathy. The record does not report the number of participants with missing evaluations or discontinuations for this endpoint, the timing of those events, or analyses under alternative assumptions. Consequently, the influence of incomplete outcome data cannot be quantified from the posted information.
The preventive-effect analysis population required random assignment, at least one dose of study drug and oxaliplatin, and at least one qualifying assessment after oxaliplatin administration. The registry record does not report a separate analysis based on all randomized participants or a detailed participant-flow account. It also does not report an interim-analysis plan, a statistical analysis plan, or the trial’s own original sample-size assumptions.
14. 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 |
|---|---|---|---|
| ART-123 (3-day ART) | 3 | 24 | 12.5% |
| ART-123 (1-day ART) | 5 | 27 | 18.5% |
| Placebo | 2 | 28 | 7.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| ART-123 (3-day ART) | 0 of 24 |
| ART-123 (1-day ART) | 0 of 27 |
| Placebo | 0 of 28 |
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 |
|---|---|
| ART-123 (3-day ART) | 24 of 24 |
| ART-123 (1-day ART) | 27 of 27 |
| Placebo | 28 of 28 |
Most frequent serious adverse event terms
| Event term | Organ system | ART-123 (3-day ART) | ART-123 (1-day ART) | Placebo |
|---|---|---|---|---|
| Metastases to liver | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 24 | 2 of 27 | 0 of 28 |
| Infective spondylitis | Infections and infestations | 0 of 24 | 0 of 27 | 1 of 28 |
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 24 | 1 of 27 | 0 of 28 |
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 24 | 0 of 27 | 0 of 28 |
| Febrile neutropenia | Blood and lymphatic system disorders | 0 of 24 | 1 of 27 | 0 of 28 |
| Enterocolitis | Gastrointestinal disorders | 0 of 24 | 1 of 27 | 0 of 28 |
| Gastrointestinal mucosal disorder | Gastrointestinal disorders | 0 of 24 | 1 of 27 | 0 of 28 |
| Fatigue | General disorders | 0 of 24 | 0 of 27 | 1 of 28 |
| Femur fracture | Injury, poisoning and procedural complications | 1 of 24 | 0 of 27 | 0 of 28 |
| Pelvic fracture | Injury, poisoning and procedural complications | 0 of 24 | 1 of 27 | 0 of 28 |
Most frequent non-serious adverse event terms
| Event term | Organ system | ART-123 (3-day ART) | ART-123 (1-day ART) | Placebo |
|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 9 of 24 | 12 of 27 | 9 of 28 |
| Stomatitis | Gastrointestinal disorders | 8 of 24 | 6 of 27 | 5 of 28 |
| Constipation | Gastrointestinal disorders | 4 of 24 | 7 of 27 | 6 of 28 |
| Diarrhoea | Gastrointestinal disorders | 5 of 24 | 5 of 27 | 5 of 28 |
| Vomiting | Gastrointestinal disorders | 2 of 24 | 2 of 27 | 4 of 28 |
| Haemorrhoids | Gastrointestinal disorders | 2 of 24 | 0 of 27 | 3 of 28 |
| Dyspepsia | Gastrointestinal disorders | 3 of 24 | 0 of 27 | 0 of 28 |
| Abdominal pain upper | Gastrointestinal disorders | 0 of 24 | 0 of 27 | 2 of 28 |
Serious events with the highest arm-level rate: metastases to liver (7.4%), metastases to central nervous system (4.2%), femur fracture (4.2%), lung neoplasm malignant (3.7%), febrile neutropenia (3.7%).
For serious adverse events, the registry lists 3 affected participants among 24 at risk in the ART-123 (3-day ART) group, 5 among 27 in the ART-123 (1-day ART) group, and 2 among 28 in the placebo group. The death count is 0 in each group. These figures describe the posted safety counts; the registry record does not provide a comparative statistical analysis of them.
The registry also reports other adverse events for all participants at risk in each group: 24 of 24 for 3-day ART, 27 of 27 for 1-day ART, and 28 of 28 for placebo. Serious and other adverse-event summaries are distinct categories in the record and should not be conflated. The listed serious-event terms with the largest reported percentages include metastases to liver (7.4%), metastases to central nervous system (4.2%), femur fracture (4.2%), lung neoplasm malignant (3.7%), febrile neutropenia (3.7%), and enterocolitis (3.7%).
These descriptive counts do not by themselves establish whether an event was caused by study treatment. The record does not provide event-level timing, severity detail beyond the serious-event classification, or adjusted comparisons among groups. The safety figures should therefore be read as reported counts rather than as estimates of a treatment-related effect.
15. What the Result Does, and Does Not, Mean
The posted results describe cumulative grade 2 or higher peripheral sensory neuropathy counts in three randomized groups. The event count was 11 for each ART-123 schedule and 18 for placebo. The unadjusted risk-difference estimates favored lower observed event proportions in the ART-123 groups, but both reported intervals include zero and the comparisons are imprecise. The p-values do not establish that the observed contrasts are real, nor do they establish that no difference exists.
This was an exploratory phase 2 study, and the registry states that no primary endpoint was specified. The result should be understood as a descriptive signal requiring cautious interpretation, not as a definitive efficacy conclusion. The record does not report the original sample-size rationale, a multiplicity plan, or alternative analyses of missing outcomes. The analysis also applies to the population defined in the endpoint description, not necessarily to every enrolled participant.
The cumulative endpoint records whether a participant ever crossed the grade threshold during the specified period. It does not indicate the duration of neuropathy, the pattern of severity over time, or an individual participant’s experience beyond the classification rule. Participants missing evaluations or discontinuing without a previously observed grade 2 or higher event were classified as not having reached the endpoint, which is important when interpreting the counts.
The registry results do not establish the cause of an event, the certainty of a treatment effect, or how these findings apply outside the studied population and design. The safety counts are descriptive and likewise do not establish treatment causation. Clinical decisions should not be inferred from these statistical summaries alone.
16. Why This Trial Matters Statistically
This study illustrates why an observed difference and a conclusive comparison are not the same thing. The ART-123 groups had lower cumulative event counts than placebo, and the risk-difference estimates were negative. Yet the intervals cross zero and are broad, so the observed data remain compatible with substantial uncertainty about the direction and size of the underlying group contrast.
The exploratory status matters statistically. The registry says that no primary endpoint was specified, while two ART-123 schedules are compared with placebo for the displayed outcome. Without a reported multiplicity strategy, the unadjusted p-values should not be interpreted as if they necessarily represent a single prespecified test. The record also does not describe an original sample-size justification, making it inappropriate to equate the observed trial size with a documented precision target.
The endpoint definition also has consequences for interpretation. A cumulative threshold classifies participants according to whether grade 2 or higher neuropathy occurred at any assessment, even if subsequent assessments were less severe. At the same time, participants with missing evaluations or discontinuation without a previously observed event were counted as not having reached the threshold. These choices shape what the event count represents.
Finally, the planning illustrations show how sample-size requirements rise when the effect targeted is smaller, under specified assumptions. They can support planning discussions, but they do not retrospectively show that the completed study had a particular power. Together, these features make the study statistically informative as an exploratory comparison while highlighting the limits of its precision and reporting.
17. 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 specific to this study affect interpretation. The registry identifies the study as exploratory and explicitly states that no primary endpoint was specified. The record lists two ART-123 schedules against placebo for the neuropathy outcome, but does not report a multiplicity adjustment or identify a confirmatory testing strategy.
The outcome analysis population required receipt of study drug and oxaliplatin and at least one eligible post-oxaliplatin evaluation. This limits direct interpretation as an analysis of every randomized participant. The registry record does not provide a participant-flow account or report how many participants were excluded from this outcome population.
The endpoint is cumulative and uses an investigator-reported grading scale. Once a participant reached grade 2 or higher, later improvement did not change the classification. Conversely, discontinuation or missing evaluation data without a prior threshold event was treated as no event. The record does not report the number affected by missingness or discontinuation, nor sensitivity analyses that could show how alternative assumptions alter the comparisons.
The listed group sizes and event counts are modest, and the reported intervals are broad. The registry record does not state the confidence level or interval-construction method. It also does not report the original statistical analysis plan, sample-size justification, randomization details, allocation concealment, or interim-analysis plan. The 42-days-after-the-start-of-cycle-12 timeframe defines the stated endpoint window, but the posted summary does not provide detailed follow-up completeness or outcome timing by group.
18. Related Tutorials
19. Related Statistical Calculators
20. Sources
- ClinicalTrials.gov: Exploratory Study of ART-123 for the Prevention of Cancer Treatment Related Symptoms in Patients With Postoperative Stage II / III Colon Cancer — NCT02792842.
- Registry record last updated 2024-04-04; status last verified 2024-03.
- Results first posted 2024-04-04.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
21. Record Summary
NCT02792842 is a completed phase 2, multicenter, randomized, double-blind, parallel-group, placebo-controlled study sponsored by Asahi Kasei Therapeutics Corporation. The record lists enrollment of 79, a start date of 2016-07, and primary completion in 2018-02. The interventions were ART-123 (3-day ART), ART-123 (1-day ART), and placebo.
The displayed outcome is cumulative NCI-CTCAE grade 2 or higher peripheral sensory neuropathy through the end of study treatment, with a stated timeframe of 42 days after the start of cycle 12. The event counts were 11, 11, and 18 in the respective groups. The comparisons are exploratory and imprecise; no primary endpoint was specified. The registry record does not report a multiplicity plan, original sample-size rationale, or confidence level for the posted intervals.