Hand Therapy Intervention Versus Traditional Occupational Therapy to Prevent Chemotherapy Induced Peripheral Neuropathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Hand Therapy Intervention Versus Traditional Occupational Therapy to Prevent Chemotherapy Induced Peripheral Neuropathy (NCT05374876), a randomized na study. The primary outcome is Number of Participants With Chemotherapy-Induced Peripheral Neuropathy (CIPN).

2. Clinical Question

The clinical question is whether the two therapy approaches differ in the recorded occurrence of hand CIPN during the stated observation period. The outcome is a participant count, rather than a measure of how severe symptoms were or how long they lasted. The comparison therefore describes the number of participants meeting the registry’s outcome definition in each arm. It does not, by itself, describe the full experience of neuropathy or establish why an outcome occurred.

The trial is identified as a pilot randomized feasibility study. Its focus and size should be kept in view when interpreting the comparison: the posted outcome counts are limited, and the interval around the recalculated difference is wide. The registry does not report a detailed clinical question about duration, severity thresholds beyond the stated CTCAE measure, or effects on daily activities as part of the primary endpoint.

3. Trial Design

NCT05374876 is recorded as a completed pilot randomized feasibility trial sponsored by HonorHealth Research Institute. The registry lists the condition as adenocarcinoma of the pancreas and describes the setting as combination chemotherapy containing albumin-bound paclitaxel and gemcitabine. The study dates recorded are 2016-05-13 for start and 2020-09-15 for primary completion. The phase is listed as NA.

The registry identifies two interventions: investigational hand therapy targeting the nervous system and traditional occupational therapy targeting compensatory strategies. Allocation is listed as randomized, with no masking in the design fields. Separately, the brief summary describes a blinded evaluator. These descriptions differ in what they say about masking; further details about the evaluator’s role or the masking procedures are not reported in the registry record. The design model is listed as single-group even though the allocation field says randomized and two intervention arms are described. The record does not explain this classification.

Enrollment is listed as 49. For the primary outcome, the arm counts are 21 in IHT and 19 in TOT. The registry does not explain the relationship between the enrollment figure and the outcome denominators, so no reason for the difference can be inferred from the record. The primary observation period runs from consent until onset of hand CIPN or through 84 days of treatment.

The registry lists 9 outcome measures and 2 analyses, including the primary participant count and secondary measures related to pain, motor function and symptoms, and nerve tolerance or irritation tests. Seven secondary outcomes are posted. Details of recruitment procedures, treatment delivery, adherence, follow-up beyond the stated endpoint window, and the protocol’s original 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.

Overall Study

Reasons for not completing this period:

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 Participants With Chemotherapy-Induced Peripheral Neuropathy (CIPN), measured over Time of consent until the time of onset of CIPN of the hands or through 84 days of treatment.

The primary endpoint counts participants reported to have chemotherapy-induced peripheral neuropathy (CIPN). The registry says CIPN was measured using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Its timeframe begins at consent and continues until CIPN of the hands begins or through 84 days of treatment. The endpoint is therefore a count of participants with the event during the stated period, not a continuous symptom score or a time-to-event estimate.

A participant count provides a direct way to describe how many people in each arm met the outcome definition. For a comparison between arms, the counts can also be expressed as risks and contrasts between those risks. Such contrasts help describe the observed difference in event occurrence, but their meaning depends on how the endpoint was defined and recorded. The registry does not report additional detail about the threshold used to classify a participant as having CIPN, adjudication procedures, or how a participant with incomplete follow-up was handled.

The outcome is clinically relevant to the trial’s stated aim of preventing chemotherapy-induced peripheral neuropathy of the hands, but the count does not capture all dimensions of neuropathy. It does not state symptom duration, change over time, or the degree of impact on function. Secondary outcomes include average hand pain and QuickDASH motor-function and symptom scores, along with findings from several nerve-related tests. Those outcomes provide different kinds of information; they should not be treated as interchangeable with the primary participant count.

The registry does not report whether the primary outcome was assessed at multiple visits or how event timing was recorded between assessments. Thus, the posted endpoint supports an account of recorded event counts over the specified window, but not a detailed reconstruction of symptom trajectories.

7. Results Posted in the Registry

• Traditional Occupational Therapy Intervention Targeting Compensatory Strategies (TOT): 21.1% (4/19) versus 28.6% (6/21) on control; risk difference -7.5 percentage points (95% CI -34.2 to 19.1), risk ratio 0.74 (0.24–2.22); unadjusted two-proportion z-test p = 0.583.

8. Statistical Interpretation

9. Statistical Methods Explained

For this endpoint, each participant is classified according to whether CIPN was reported during the stated observation period. This is a binary outcome at the participant level: an event is counted or it is not. The primary summary is therefore a count in each arm. A risk is the count with the event divided by the number assessed in that arm. Comparing those risks describes the absolute difference in event occurrence between groups.

What does the risk difference describe?

The risk difference is an absolute contrast: it subtracts one arm’s event risk from the other arm’s event risk. Its sign depends on the order of the arms. In this comparison, TOT is contrasted with IHT, so a negative estimate indicates a lower observed event proportion in TOT. The estimate is based on the posted arm counts and is unadjusted. It does not account for participant characteristics or other factors that could influence outcomes.

An interval around a risk difference represents uncertainty in the estimate. If the interval includes zero, values consistent with no absolute difference are among the values compatible with the data and the interval method. Here, the interval spans negative and positive values. That means the observed counts do not pin down the direction of the underlying difference with precision. The interval is broad relative to the estimate, so a range of materially different contrasts remains compatible with the data.

How should p-values be read?

A p-value is calculated under a null hypothesis and a statistical model. It summarizes how unusual results at least as discrepant as the observed results would be if that null model applied. It is not a measure of effect size, clinical importance, or the chance that the null is correct. A larger p-value does not prove that groups are equal. In a small trial, limited information can make it difficult to distinguish a real difference from chance variation.

The recalculated p-value of 0.583 comes from an unadjusted calculation using the posted summary counts. The registry separately reports a chi-squared analysis with p = 0.721. A chi-squared test is a general method for assessing whether categorical outcome frequencies differ across groups. Its result depends on the test specification and the data used. The registry does not report enough detail to reconstruct the sponsor’s analysis or explain the difference between the two p-values. They should be identified as separate analyses rather than blended into one result.

What do relative measures add?

A risk ratio compares the event risk in one arm with the event risk in the other. An odds ratio compares the corresponding odds. Both are relative measures, and a ratio of one represents no relative contrast. Their intervals extend across the null value, indicating uncertainty about whether the relative association favors one arm or the other. Relative measures can be harder to interpret when event counts are small; their scale also differs from the absolute risk difference. Reporting one type does not remove uncertainty in the other.

All these measures are calculated from the same arm-level outcome information and therefore are not independent confirmations. The primary event counts remain the foundation for interpretation. Neither the relative measures nor the p-values adjust for possible differences between participants, and the registry does not report an adjusted primary analysis.

Why does small-sample uncertainty matter?

With limited numbers of participants and events, each outcome contributes noticeably to the group totals. Estimates can consequently vary substantially if only a small number of outcomes differ. Confidence intervals convey this sampling uncertainty more directly than a single p-value or point estimate. They do not account for every possible source of uncertainty, such as outcome misclassification, incomplete follow-up, or differences in treatment delivery.

General statistical context: binary outcomes are often analyzed with methods based on a binomial model, in which the event probability is estimated separately for each group. The appropriateness of a particular test or interval method depends on the design and data. The registry does not identify the method used for its reported chi-squared result beyond naming that test, and it does not report a complete statistical analysis plan. The unadjusted recalculation should therefore be understood as a descriptive comparison based on the posted counts, not as a reconstruction of every planned or sponsor-conducted analysis.

General statistical context: multiplicity arises when several outcomes, comparisons, or analyses are examined. If many statistical tests are conducted, the chance of at least one apparently notable result can increase unless the analysis plan addresses that issue. The registry lists 9 outcome measures, posts 7 secondary outcomes, and identifies 2 analyses, but does not report whether or how multiplicity was handled. The primary and secondary results should not be interpreted as a single, fully specified family of tests without that information.

10. Confidence Intervals and Precision

The recalculated risk difference is accompanied by an interval whose lower bound is negative and upper bound is positive. Because zero lies within that interval, the results do not precisely determine whether the event risk is higher in IHT or in TOT. The interval is wide, leaving considerable uncertainty about the absolute size of any difference. The relative-effect intervals likewise span their null value, reinforcing that the observed data do not tightly establish the direction or magnitude of the comparison.

General statistical context: a confidence interval is a range produced by a statistical procedure intended to reflect uncertainty in an estimate. A narrower interval indicates greater precision under that procedure; a wider interval indicates less precision. An interval is not a guarantee that the true effect lies inside it, and it does not include every source of uncertainty. The registry does not state the confidence level for the recalculated intervals, so a particular coverage percentage should not be assigned to them.

The limited arm counts and event counts contribute to imprecision. The point estimate is only one summary of these data; the interval shows that substantially different underlying contrasts remain plausible. The reported p-values do not replace this information. In particular, a result that is not statistically significant does not demonstrate equivalence, and an interval spanning the null does not show that the two interventions have identical effects.

Precision also depends on the quality and completeness of outcome ascertainment. The registry specifies CTCAE version 4.0 and the observation window, but it does not report missing-outcome handling, assessment schedules, or further adjudication details. Those omissions limit the ability to assess uncertainty arising from measurement and follow-up in addition to sampling variability.

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.

The planning figures are participants per arm, not total events. They are illustrations based on the observed effect rather than the trial’s own original design assumptions. The stated planning assumptions 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. The trial’s original sample-size assumptions and justification are not reported in the registry record.

For 100% of the observed effect, the illustration gives 517 participants per arm for 80% power and 692 participants per arm for 90% power. For 75% of the observed effect, it gives 943 participants per arm for 80% power and 1,262 participants per arm for 90% power. For 50% of the observed effect, it gives 2,173 participants per arm for 80% power and 2,908 participants per arm for 90% power.

In plain terms, the 80% power column gives the planned number per arm under the stated assumptions for a design with an 80% chance of detecting the specified effect if that effect were the true one and the assumptions held. The 90% column uses the corresponding 90% target. A smaller effect is harder to distinguish from random variation, so the planning illustration requires more participants per arm as the target effect becomes smaller.

These figures are not observed power for this trial. They are planning illustrations calculated from the observed contrast, and the observed estimate is uncertain. If the true effect differs from that estimate, the sample sizes needed for planning would differ as well. The registry does not report whether the trial’s original design used these assumptions or these target sizes.

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 z_1−α/2 = 1.960) and the desired power (z_1−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

1. Control proportion p₀ = 0.286; treatment proportion p₁ = 0.211; average p̄ = 0.248.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6108 = 1.1972.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6085 = 0.5121.
4. n = (1.1972 + 0.5121)² / (-0.0752)² = 516.8, rounded up to 517 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 <- 0.285714285714286                          # control proportion
p1 <- 0.210526315789474                          # 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(5374876)
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 = 517 (80% power), 692 (90% power)
 75% of observed effect: n per arm = 943 (80% power), 1,262 (90% power)
 50% of observed effect: n per arm = 2,173 (80% power), 2,908 (90% power)
power.prop.test: 516.8 
Simulated power at n = 517 per arm: 0.804 (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. Analyses Reported by the Sponsor

The registry reports the sponsor’s analysis as a chi-squared test, with p = 0.721. It does not provide an effect estimate or interval from that analysis, nor does it give the test statistic or further details of the calculation. The sponsor’s result is therefore best described as the posted chi-squared p-value, rather than as a fully specified estimate of the difference between arms.

The unadjusted recalculation from the posted counts gives p = 0.583 and includes a risk-difference estimate and interval. This is a separate calculation, not a replacement for or reconstruction of the sponsor’s test. The recalculation makes the direction and uncertainty of the absolute contrast more explicit, while the registry’s reported analysis supplies the sponsor’s own test result. The record does not identify a discrepancy between them, but it also does not explain why the p-values differ.

Neither p-value establishes equivalence or settles the clinical question. The sponsor’s analysis and the recalculation both need to be read in light of the small posted arm counts and the wide interval around the recalculated contrast. Further details of the sponsor’s analysis and the original analysis plan are not reported in the registry record.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures and posts 7 secondary outcomes, in addition to the primary participant count. The secondary outcomes include average hand pain, QuickDASH motor function and symptoms, and counts of positive or negative findings from several nerve-related tests. These outcomes address different aspects of symptoms and examination findings, so they are not substitutes for the primary count of CIPN events.

The record identifies 2 analyses but does not explain how the primary and secondary analyses relate to one another, whether there were additional comparisons, or whether a particular outcome was designated as the sole primary analysis in a full protocol. A prespecified hierarchy, adjustment for multiple testing, or other multiplicity strategy is not reported in the registry record. General statistical context: when many outcomes or tests are examined, a result can appear notable by chance more often than when only one test is conducted. Without a stated approach, secondary results should be treated as exploratory rather than as independent confirmatory evidence.

Missing-data handling is not reported. The registry does not say how participants with incomplete outcome assessments were handled, whether participants who stopped treatment remained in the analysis, or whether any imputation or sensitivity analysis was used. Enrollment is listed as 49, while the primary outcome arm denominators are 21 and 19; the record does not explain this relationship. It is not possible to determine from the posted information whether the outcome counts represent all randomized participants or a subset defined by follow-up or analysis eligibility.

Analysis populations are also not described. The registry does not state whether the primary comparison used an intention-to-treat population, a per-protocol population, or another group. Random allocation is listed, but allocation concealment and details of implementation are not reported. These omissions make it difficult to assess how closely the posted comparison preserves the randomized design or how missing outcomes might affect the estimate.

15. 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.

The registry reports zero serious adverse events in the IHT arm among 21 participants at risk and zero in the TOT arm among 19 participants at risk. It also reports zero other adverse events in each arm, using the same respective at-risk counts. Deaths are reported as zero in both arms, and no top serious-event terms are listed.

These figures describe the adverse-event counts posted in the registry for the reported groups. They do not establish that no adverse events of any kind occurred outside the categories or reporting period captured by the record, and they do not show that either therapy is risk-free. The registry does not provide detailed definitions, ascertainment procedures, event timing, or a narrative account of safety monitoring.

With these arm counts, zero reported events should be interpreted as an observation in this trial, not as proof that an event cannot occur. The posted figures also do not by themselves support a comparative safety conclusion. The record does not report a formal statistical comparison of adverse events between the interventions.

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

The posted primary results record CIPN in 6 participants assigned to IHT and 4 assigned to TOT. The unadjusted recalculation gives a negative risk difference for TOT relative to IHT, but its interval crosses zero and is wide. The recalculated p-value is 0.583; the sponsor’s reported chi-squared p-value is 0.721. Together, these results show that the available counts do not precisely resolve the direction or size of the difference between the arms.

This does not mean that the interventions are equivalent. Establishing equivalence or non-inferiority requires an appropriate design and a prespecified margin, neither of which is reported in the registry record. Nor do the posted results establish that one approach prevents CIPN better than the other. A non-significant test is not proof of no effect, and the point estimate alone is not a dependable summary of what would occur in a larger population.

The primary endpoint is a count of participants meeting the CIPN outcome definition within the stated observation window. It does not describe symptom severity, duration, progression, or every effect on daily function. Secondary outcomes concern pain, motor function and symptoms, and nerve-related examination findings, but the registry posts only 7 of the listed secondary outcomes and gives limited analysis detail. Those outcomes cannot be used to fill gaps in the primary endpoint’s interpretation.

The pilot feasibility designation is important context. These results are an initial comparison based on modest arm counts, not a definitive estimate of comparative effects. The planning illustration suggests that much larger group sizes would be needed under its assumptions to target the effects listed, but those calculations use the observed effect and should not be treated as the original trial’s design rationale.

Finally, the record does not describe missing-data procedures, analysis populations, or a multiplicity plan. Those gaps limit interpretation of the posted estimates and any secondary findings. The results should therefore be read as a description of the recorded outcomes in this trial, with substantial uncertainty, rather than as a conclusive answer to the broader question of prevention.

17. Why This Trial Matters Statistically

This trial illustrates an important distinction between an observed difference and a precise estimate of an underlying effect. The arm counts produce a directional contrast, but the interval is broad and includes values on both sides of no absolute difference. A point estimate alone could make the comparison seem more conclusive than the data support; the interval communicates how much uncertainty remains.

It also shows why a p-value should not be used as a verdict. The sponsor’s chi-squared result and the unadjusted recalculation are both non-significant, but neither demonstrates that the interventions have the same effect. Conversely, the direction of the recalculated estimate does not prove a difference. Effect size, uncertainty, design, and measurement all matter alongside statistical testing.

The trial is designated as a pilot feasibility study, and that context affects what can reasonably be learned from its results. A pilot can contribute early evidence about how an intervention comparison is recorded and can inform further study, but the registry does not report its original sample-size justification or detailed feasibility outcomes. The planning figures illustrate how strongly required sample size can depend on the effect a future study aims to detect.

Finally, clear reporting of analysis populations, missing data, multiplicity, and outcome procedures is essential for judging what a randomized comparison represents. Several of those details are not reported in the registry record. Recognizing such limits is not a criticism of the observed counts; it is part of interpreting them accurately and distinguishing descriptive evidence from a definitive comparative conclusion.

18. 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 leaves several trial-specific questions unanswered. Although allocation is listed as randomized and two intervention arms are described, the design model is listed as single-group. The record does not explain this classification. It also lists no masking, while the brief summary describes a blinded evaluator. The scope of evaluator blinding and any procedures used to maintain it are not reported.

Enrollment is recorded as 49, while the arm denominators for the primary outcome are 21 and 19. The registry does not explain the difference or state which analysis population those denominators represent. Missing outcome data, participant withdrawals, adherence, treatment exposure, and analysis by randomized assignment are not described. These details matter for understanding whether the arm counts capture the randomized groups comparably.

The endpoint timeframe is stated, and CTCAE version 4.0 is named, but further information about assessment timing, event ascertainment, and classification procedures is not reported. The record does not describe how participants with incomplete observation through 84 days were treated. Nor does it report an adjusted analysis, the full analysis plan, or the confidence level for the recalculated intervals.

Several secondary outcomes are listed, but only 7 are posted, and the registry does not report a multiplicity strategy. The sponsor’s analysis is named as chi-squared, but details needed to reproduce it are absent. The original sample-size assumptions and justification are also not reported. Taken together with the limited primary outcome counts and wide interval, these reporting gaps constrain how fully the comparison can be evaluated.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Hand Therapy Intervention Versus Traditional Occupational Therapy to Prevent Chemotherapy Induced Peripheral Neuropathy — NCT05374876.
• Registry record last updated 2026-07-08; status last verified 2026-04.
• Results first posted 2026-07-08.
• 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.

22. Record Summary

NCT05374876 is a completed pilot randomized feasibility trial sponsored by HonorHealth Research Institute. It compares investigational hand therapy targeting the nervous system with traditional occupational therapy targeting compensatory strategies among people with pancreatic adenocarcinoma receiving albumin-bound paclitaxel and gemcitabine-containing combination chemotherapy.

The primary endpoint counts participants with CIPN of the hands, measured using CTCAE version 4.0 from consent until onset or through 84 days of treatment. The registry lists 49 enrolled participants and reports primary outcome counts of 6 among 21 in IHT and 4 among 19 in TOT. Its reported chi-squared analysis has p = 0.721; the unadjusted recalculation has p = 0.583 and a wide risk-difference interval spanning zero. The record does not report detailed missing-data methods, analysis populations, multiplicity handling, or the original sample-size rationale.