NR in Chemo-induced Peripheral Neuropathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for NR in Chemo-induced Peripheral Neuropathy (NCT03642990), a na phase 2 study. The primary outcome is Number of Participants With No Worsening in the Grade of Peripheral Sensory Neuropathy as Scored by CTCAE.

2. Clinical Question

The trial asked whether nicotinamide riboside (NR) could help prevent worsening of peripheral sensory neuropathy in patients receiving paclitaxel or nab-paclitaxel. It was a single-group study, so the clinical question was about the observed experience during NR treatment rather than a comparison with a concurrent control group. The registry record does not report a primary outcome count or an estimate of the proportion whose neuropathy did not worsen.

The conditions listed in the record cover several cancer settings, while the intervention description concerns NR taken alongside paclitaxel or nab-paclitaxel treatment. Because there is no like-for-like control group, the record cannot establish how neuropathy would have changed over the same period without NR. It also does not report a primary outcome estimate that would describe the observed course within the treated group.

3. Trial Design

This was a phase II, single-group trial of nicotinamide riboside in patients receiving paclitaxel or nab-paclitaxel. The registry lists enrollment as 5 and the study status as terminated. The record gives a start date of 2019-11-08 and a primary completion date of 2021-08-18. The reason for termination is not reported in the registry record.

The intervention was daily oral NR. The planned regimen began with 300 mg daily, divided between morning and evening, for one week, followed by an increase to 1000 mg daily, also divided between morning and evening, for the remaining 11 weeks. The brief description frames the aim as preventing progression of peripheral sensory neuropathy during chemotherapy. The primary outcome timeframe is approximately 4 weeks; the record does not explain how this timeframe relates to the planned treatment duration.

There was no random allocation and no masking. The registry describes the model as single group and allocation as not applicable. These design features mean that the study does not provide a randomized comparison between NR and another treatment or a no-NR control. Any observed change during the trial could reflect the course of neuropathy during chemotherapy, other influences on symptoms, or NR; the single-group design cannot separate these explanations.

The registry describes the primary outcome population as the 4 subjects who took at least one dose of NR. The record also lists 5 participants at risk for the adverse-event summaries. These are different descriptions tied to different outcomes; the record does not provide further detail that would reconcile the populations or explain all participant disposition. The protocol’s sample-size justification, detailed statistical plan, and reason for stopping 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: Seven subjects were screened for enrollment, of whom two were ineligible.

300 mg/Day for One Week

Reasons for not completing this period:

1000 mg/Day for Weeks 2-12

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Data are reported for the 4 subjects who took at least one dose of NIAGEN. End of treatment was originally defined as within 2 weeks after 12 weeks of NIAGEN treatment ended (i.e. a study duration of \~14 weeks). If a patient withdrew before completing 12 weeks of treatment, the end of treatment was designated as one week after withdrawal from the study. The longest that any participant was on NIAGEN was three weeks. Therefore, the time frame of the study has been adjusted to \~4 weeks.

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 No Worsening in the Grade of Peripheral Sensory Neuropathy as Scored by CTCAE, measured over approximately 4 weeks.

The primary endpoint is the number of participants with no worsening in the grade of peripheral sensory neuropathy, scored using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. The record describes sensory symptoms and reflex findings at grade 1, moderate symptoms limiting instrumental activities of daily living at grade 2, and severe symptoms limiting self-care activities of daily living at grade 3. The endpoint therefore focuses on whether the recorded neuropathy grade worsened, rather than on a change in a continuous symptom score.

A categorical endpoint can make a clinically interpretable distinction between a participant whose grade worsens and one whose grade does not. It can also be straightforward to report as a count. However, reducing changes to a worsening/no-worsening classification does not show how large a change was, and it may not capture changes that occur without crossing a grade boundary. Those are general features of categorical outcomes, not additional findings from this trial.

The registry record contains an ambiguity in its wording: the endpoint title refers to no worsening, but the description says the outcome was recorded as “yes” when it worsened and “no” when it did not worsen. The count corresponding to the primary endpoint is not reported in the registry record, so the observed result and its precision cannot be assessed from the posted information. The specified timeframe is approximately 4 weeks.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with the outcome’s scale and the design that generated it. The primary endpoint is a count of participants classified according to whether neuropathy worsened. It is not a continuous score, time-to-event outcome, or comparison between randomized groups. The study is single group, so any estimate based on this endpoint would describe the observed participants receiving NR rather than a contrast between NR and a control strategy.

What would a count describe?

For a binary outcome, each participant is assigned to one of two categories, such as worsening or no worsening. The count in a category conveys how many participants were classified that way. A proportion would relate that count to the relevant analysis population, while a confidence interval would describe uncertainty around an estimated quantity under the assumptions of the statistical method. These are general concepts. In this record, the primary outcome count and any corresponding estimate or interval are not reported, so none can be interpreted.

The wording of the endpoint also warrants care. Its title is phrased as the number with no worsening, whereas the description says “yes” means the grade worsened and “no” means it did not. A reader needs the outcome coding to be clear before interpreting a reported category count. The registry record does not give a primary result that would resolve this wording issue.

What does a single-group design permit?

A single-group study can describe outcomes among participants who received the intervention. It does not by itself estimate the difference between intervention and control outcomes. In a randomized comparison, allocation can help make groups comparable on average; this trial had no randomized allocation and no separate comparator. Changes over time could be associated with NR, chemotherapy exposure, the underlying clinical course, or other influences. Without a concurrent comparison, those possibilities cannot be disentangled statistically.

Masking is listed as none. In general, knowledge of treatment or assessment can affect how subjective symptoms are reported or judged. The primary endpoint uses a grade-based assessment, and the registry describes symptom and activity limitations as part of that grading. The record does not provide information about blinded outcome assessment, so no further claim about safeguards against assessment bias is possible.

How should uncertainty be understood?

A confidence interval is a range calculated by a statistical procedure to express uncertainty around an estimate. Its width depends on the amount and variability of information and on the method’s assumptions. A small analysis population generally leaves limited information for estimating an outcome precisely; it does not justify treating an unreported estimate as either favorable or unfavorable. Because the primary count and interval are absent, the precision of the primary result cannot be assessed.

For binary data, methods may use approximations or methods designed for sparse counts. General statistical practice considers whether an approximation is suitable for the available data. The registry record does not report an analysis method for the primary endpoint, and the number of analyses is listed as 0. It is therefore not possible to identify a sponsor-reported inferential method, an adjusted estimate, or a formal test for this outcome.

What are planning illustrations?

Sample-size calculations are planning tools: they describe how much information a future study might need under stated assumptions. They are not observed power and do not increase the information in the participants already studied. The planning assumptions described for the illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is framed as a stated fraction of an observed effect. These assumptions are illustrative and are not reported as the design plan for this single-group trial. In particular, the trial itself had no two-arm allocation, so such calculations should not be read as a description of its design.

For a binary outcome, planning results expressed as participants per arm are hypothetical requirements under the calculation’s assumptions, not observed enrollment or evidence that a study had a given chance of detecting an effect. The record does not report the trial’s own sample-size justification. Since the primary outcome result is also absent, the posted information does not support an independent assessment of the observed primary effect that could ground a planning comparison.

Why can extra variability matter?

Over-dispersion is a general statistical issue in count data: observed variability may exceed what a chosen model assumes. When that occurs, standard errors and intervals from a model that assumes less variability can be too small, making estimates appear more precise than warranted. The primary outcome is a participant count with a binary classification, not a reported repeated count process. The record does not report an over-dispersion assessment or a model for the primary outcome, so this concept should not be mistaken for a finding from the trial.

Statistical methods can clarify uncertainty only when the outcome data, analysis population, and method are adequately described. The registry record states the endpoint definition and identifies the primary outcome population, but does not report the primary result or its analysis. The most defensible interpretation is therefore descriptive: the trial’s design and intended measure can be explained, while an effect estimate and its precision cannot be reconstructed from the record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("NIAGEN®)")
n      <- c(4)
events <- c(3)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  NIAGEN®)  4  3  75.0  19.4  99.4  30.1  95.4  28.4  94.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures and gives several secondary outcomes, including paclitaxel or nab-paclitaxel dose reductions, dose reduction events, total paclitaxel dose, and a change in the FACT&GOG-NTX subscale score. Considering multiple outcomes can raise the chance of finding an apparently notable result by chance when many statistical tests are conducted. This is the general issue of multiplicity. The registry record does not report a multiplicity adjustment, a hierarchy for interpreting outcomes, or a statistical analysis plan explaining how multiple outcomes were to be handled.

The number of analyses is listed as 0, and no primary outcome estimate or test is reported. The absence of a reported analysis should not be interpreted as evidence that no analysis was conducted; it means that inferential results are not available in the registry record. The record also does not report whether analyses were prespecified, adjusted for covariates, or conducted at interim time points.

For the primary outcome, the record identifies 4 subjects who took at least one dose of NR. It does not fully report the analysis population rules or provide a complete account of participant disposition for that endpoint. The description says end of treatment was originally defined as within 2 weeks after 12 weeks of treatment ended, and notes a different circumstance for participants who withdrew before completing treatment. Further details about how such participants were classified or included are not reported in the registry record.

Missing outcome data can affect both the estimated result and its interpretation, especially if the availability of an assessment is related to participant experience. The registry record does not report the amount, reasons, or statistical handling of missing primary outcome data. No assumption about missing observations, imputation, or sensitivity analysis can therefore be attributed to the study.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists safety information for the NIAGEN® group. Among the 5 participants at risk for these summaries, 0 are listed as having a serious adverse event and 4 as having other adverse events. The record also lists 1 death. These are counts, not comparative estimates, and there is no separate control group against which to compare them.

The serious-event count does not show the nature, timing, duration, or cause of events beyond what is separately recorded. No top serious-event terms are listed. The record does not state whether the death was related to treatment, occurred during treatment, or had another cause. It would be inappropriate to infer any of those details from the count alone.

Adverse-event summaries describe events recorded in the study; they do not, on their own, establish that the intervention caused an event or that it did not cause one. Attribution, follow-up completeness, and definitions used for collection can all affect interpretation. Those details are not reported in the registry record. The figures should therefore be read narrowly as the posted counts, without converting them into a claim about comparative safety or causation.

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

The registry record establishes that this was a phase II, single-group trial of daily NR during paclitaxel or nab-paclitaxel treatment, and that the planned primary measure concerned worsening in the grade of peripheral sensory neuropathy. It also identifies a primary outcome population of 4 subjects who took at least one dose. These details define the clinical question and the kind of observation the study was intended to make.

However, the primary outcome result is not reported in the registry record. There is no count showing how many participants had no worsening, and no estimate or interval showing the precision of such a result. Without that information, the posted results cannot quantify the observed primary outcome. Even if a count were available, the single-group design would still not show what would have happened under a control strategy.

The design does not support attributing a change in neuropathy to NR alone. Neuropathy can be observed during chemotherapy, and a single-group study has no concurrent comparator to separate the intervention from the treatment course or other influences. This is a general limitation of the design, not evidence for or against an effect.

The adverse-event counts are likewise descriptive. The record lists no serious adverse events, other adverse events among 4 participants, and 1 death, but does not provide enough information to interpret the death’s cause or relationship to treatment. The study’s terminated status is known; the reason is not reported in the registry record. Neither the termination status nor the safety counts fill the gap in the primary endpoint result.

Accordingly, the record documents the study’s aims, regimen, design, and selected safety counts, but it does not establish whether NR prevented worsening of neuropathy. It also does not establish that NR failed to do so. Those conclusions would require outcome information and, for a comparative treatment effect, an appropriate comparator and analysis.

14. Why This Trial Matters Statistically

This trial illustrates how a clearly stated clinical question and a reported outcome definition are not enough to support an effect estimate when the result itself is missing. The registry describes a binary primary endpoint based on neuropathy grade, but does not give the count classified as having no worsening. Without the observed outcome, readers cannot evaluate either the direction or the precision of the primary result.

The design also highlights the difference between describing an outcome and estimating a treatment effect. A single-group study can record what occurred among participants who received NR, but it cannot provide a concurrent counterfactual comparison. In clinical research, the distinction matters: within-group observations may be informative about feasibility or experience, yet they do not by themselves show what difference an intervention made.

The record’s small primary outcome population makes transparent reporting especially important. Counts, analysis populations, missing-data handling, and uncertainty estimates allow readers to understand how much information underlies a result. Here, the registry identifies 4 subjects in the primary outcome population but does not report the endpoint count, analysis method, or precision. The safety summaries are available as counts, but they answer a different question from the primary neuropathy endpoint.

Finally, the terminated status raises a reporting question without answering it. The reason for termination is not reported in the registry record, so the status cannot be used to infer a safety concern, an efficacy finding, or an operational problem. This case underscores the statistical value of complete outcome reporting and clear explanations of study conduct: design, outcome data, and analysis details each contribute different information, and none can substitute for the others.

15. 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 most direct limitation is that the primary endpoint result is not reported in the registry record. Although the endpoint definition and primary outcome population are described, the record does not state the count of participants with no worsening, the corresponding count with worsening, or an uncertainty estimate. The primary outcome’s wording also pairs a title about no worsening with a description in which “yes” means worsening, so the coding would need clarification alongside any reported result.

The single-group design has no concurrent control, no randomized allocation, and no masking. It cannot distinguish changes associated with NR from changes associated with chemotherapy, the underlying clinical course, or other factors. The record does not report a detailed statistical plan, a sample-size justification, interim analyses, or the reason the trial was terminated.

The primary outcome population is described as the 4 subjects who took at least one dose, while the safety summaries list 5 participants at risk. The registry does not provide a full disposition account explaining the populations or the extent of missing endpoint assessments. It also does not report how withdrawals, incomplete treatment, or missing outcome data were handled in the analysis.

The primary outcome timeframe is approximately 4 weeks, while the intervention regimen is described across 12 weeks. The registry gives some end-of-treatment timing information but does not fully explain the relationship between the endpoint timeframe and treatment schedule. Finally, adverse-event counts do not include enough information about timing or attribution to support causal interpretation, and the listed death lacks reported context.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: NR in Chemo-induced Peripheral Neuropathy — NCT03642990.
• Registry record last updated 2023-04-12; status last verified 2023-03.
• Results first posted 2023-04-12.
• 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.

19. Record Summary

The registry record describes a phase II, terminated, single-group trial of daily oral nicotinamide riboside during paclitaxel or nab-paclitaxel treatment. The planned dose was 300 mg daily for one week, followed by 1000 mg daily for the remaining 11 weeks. Enrollment is listed as 5, and the primary outcome population is described as 4 subjects who took at least one dose.

The primary endpoint was the number of participants with no worsening in CTCAE-graded peripheral sensory neuropathy, with a timeframe of approximately 4 weeks. Its result, analysis method, and precision are not reported in the registry record. The record lists 0 serious adverse events, other adverse events for 4 participants, and 1 death, without enough context to determine cause or attribution. The reason for termination is not reported.