Vitamin B12 for Aromatase Inhibitors Musculoskeletal Symptoms: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vitamin B12 for Aromatase Inhibitors Musculoskeletal Symptoms (NCT03069313), a na na study. The primary outcome is Percentage Change in Average Joint Pain in Women With Aromatase Inhibitor-associated Musculoskeletal Symptoms (AIMSS) Compared to Baseline as Measured by the Brief Pain Inventory Short Form (BPI-SF)..

2. Clinical Question

This design can describe change over time among participants who received the intervention, but it cannot by itself separate a treatment-associated change from other explanations. Without a concurrent comparison group, the study does not directly estimate how pain would have changed over the same period without vitamin B12. The registry record does not report a causal comparison or a control-group result.

3. Trial Design

The registry lists this study as a single-group investigation of oral vitamin B12 for aromatase inhibitor-associated musculoskeletal symptoms in women with early-stage breast cancer. Its official title calls it a single-arm phase II study, while the phase entry is NA. The registry records allocation as NA and masking as NONE. No randomized or masked comparison is described.

The only listed arm is Arm I, described as oral vitamin B12. The registry classifies vitamin B12 as a dietary supplement. It does not report the dose, dosing schedule, adherence assessment, permitted co-interventions, or criteria for changing or stopping treatment. The comparator is not reported in the registry record because the design is single group.

The primary outcome was assessed at baseline and 90 days (+/- 10 days). The registry record states that forty-one patients enrolled, five withdrew, and thirty-six completed the study. It does not explain the reasons for withdrawal or say whether all enrolled participants contributed data to the primary analysis.

The study is recorded as completed. The start date is 2015-10-19 and the primary completion date is 2016-10-27. Texas Tech University Health Sciences Center, El Paso is listed as sponsor. These registry entries describe the study structure, not its effectiveness: the primary endpoint result, its uncertainty, and the statistical test result are not reported in the registry record.

A single-group baseline-to-follow-up design can show the pattern of measurements over time in the observed participants if those results are reported. However, changes could also reflect factors such as symptom fluctuation, changes in other care, or the passage of time. These are general interpretive considerations, not events established for this study. A concurrent comparison group would be needed to make a direct between-group contrast, and none is listed.

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: IRB approved recruitment of 50 participants

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: A total of forty-one patients were enrolled, five patients withdrew, leaving thirty-six patients to complete the study.

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 Percentage Change in Average Joint Pain in Women With Aromatase Inhibitor-associated Musculoskeletal Symptoms (AIMSS) Compared to Baseline as Measured by the Brief Pain Inventory Short Form (BPI-SF)., measured over Baseline and 90 days (+/- 10 days).

The primary endpoint is the percentage change in average joint pain compared with baseline, measured with the Brief Pain Inventory Short Form (BPI-SF). The scheduled follow-up is 90 days (+/- 10 days). The registry description says participants were asked to rate average pain within the last 24 hours. The stated scale runs from 0, indicating "No pain," to 10, indicating "Pain as bad as you can imagine."

Average pain is a patient-reported measure of symptom intensity. It focuses the primary question on joint pain associated with aromatase inhibitor use, rather than on a laboratory measure or a broader measure of well-being. Comparing a follow-up pain score with baseline is intended to describe change during the study period. Percentage change expresses that change relative to the baseline value; it does not, on its own, establish why the change occurred.

The registry description states an expectation of at least 20% improvement in BPI-SF pain scores. This is an expectation, not a reported finding. The primary result, including the observed mean percentage change and its standard deviation, is not reported in the registry record. The record also does not report a confidence interval or a statistical test result for this endpoint.

Self-reported pain can capture a symptom that matters directly to participants, but it is subject to ordinary variation in how a person experiences and rates pain. In general, interpreting a change also depends on the scale’s measurement properties, baseline values, missing follow-up data, and the analysis method. Details on these matters beyond the scale description are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is a continuous outcome: percentage change in average joint pain on the BPI-SF. For a continuous outcome, a mean describes the central tendency of the measured values, while a standard deviation describes their spread. Reporting both can help readers distinguish an average pattern from how consistently participants’ measurements cluster around it. The registry identifies mean and standard deviation as the summary type, but does not report their primary endpoint values.

What does a baseline-to-follow-up change estimate?

In general, a within-participant change compares a person’s follow-up measurement with that person’s own baseline measurement. Summarizing such changes can describe the course of the measured outcome among participants with usable measurements. It is different from comparing separate treatment groups, because it does not subtract the change in a concurrent control group from the change in the intervention group. The registry lists only one group, so the design does not provide that controlled contrast.

A percentage change places a change in relation to the baseline measurement. This can be useful when the question concerns relative rather than absolute change, but interpretation depends on the baseline value and on how the percentage is defined and analyzed. The precise calculation procedure is not reported in the registry record. No new estimate can be recovered from the listed description alone.

How should a confidence interval be understood?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under a specified model and its assumptions. A narrower interval indicates greater precision than a wider interval for the same estimand, but it does not remove bias from a weak design or make an uncontrolled comparison causal. The primary endpoint’s confidence interval is not reported in the registry record. The registry record also does not report the statistical test or analysis model used for the primary outcome.

A p-value, when reported, addresses how compatible the observed data are with a specified null model, subject to the analysis assumptions. It does not measure the size or practical importance of an effect, and it does not give the probability that a treatment is effective. The primary endpoint p-value is not reported in the registry record, so no claim about statistical significance can be made from the information listed.

Why does the single-group design matter?

In a single-group study, the observed follow-up measurement can be compared with baseline, but there is no concurrent group to represent what might have happened over the same period without the intervention. General influences such as symptom fluctuation, expectation, or changes in other care can affect before-and-after measurements. A design with random allocation to comparison groups can, under appropriate conditions, better support a causal contrast; this study is not described as randomized and lists no comparator. These are general design principles, not evidence that any particular influence changed the study’s measurements.

The registry record describes the intervention as oral vitamin B12 but does not report details such as dose, adherence, or concurrent treatment. Those details can matter when interpreting how an intervention was implemented and how closely participants followed it. The absence of such information in the registry record prevents assessment of those features.

What do the planning illustrations mean?

The registry’s stated planning illustration uses 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. It is described as a planning calculation based on the observed effect, not as the original trial design. Because the study itself is single group, the illustration’s equal-allocation, two-arm setup is hypothetical and should not be mistaken for the design actually used.

Sample-size calculations describe how many participants a hypothetical design would require under specified assumptions. They do not report an observed trial effect, and they are not observed power. Power is a design property under assumptions about the true effect, variability, significance level, and analysis; calculating it from an observed effect after a study is not a reliable way to establish what the study could detect. The numerical planning results are not reported in the registry record, and no new values are calculated.

Why can variability matter?

For a continuous symptom measure, greater variability makes it harder to estimate a mean precisely, all else equal. If measurements are more dispersed than an analysis assumes, standard errors and confidence intervals can be misleading. General methods can address certain forms of extra variability, but the appropriate approach depends on the data structure and model. The registry record does not report whether over-dispersion was assessed or whether any adjustment was used. The outcome is described with a mean and standard deviation; the underlying distribution and diagnostic checks are not reported.

These statistical concepts explain how a result might be interpreted, but they cannot fill in missing study results. The registry record does not report the primary estimate, its uncertainty, the analysis population, or the complete statistical plan. Consequently, the design and measurement can be described, while the primary statistical finding cannot be evaluated from the registry information.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Arm I")
n   <- c(36)
m   <- c(-33.8)
sp  <- c(34.1)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Arm I  36  -33.800  34.100  -45.338  -22.262

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and seven analyses. The primary measure concerns percentage change in average joint pain. Listed secondary outcomes concern worst pain, functional quality of life measured by the FACT-ES, and percentage changes in serum vitamin B12, C-reactive protein, homocysteine, and methylmalonic acid. The record does not explain how the analyses correspond to each outcome or which analysis was designated for each secondary measure.

When multiple outcomes or statistical tests are examined, the chance of at least one apparently unusual result can rise. In general, a prespecified testing hierarchy or a multiplicity adjustment can help control that issue, but the choice depends on the scientific aims. Whether the study used a multiplicity adjustment, a hierarchy, or another approach is not reported in the registry record. No secondary outcome results are reported, so their consistency or relationship to the primary measure cannot be evaluated.

The primary outcome description states that forty-one patients enrolled, five withdrew, and thirty-six completed the study. The record does not report why participants withdrew, how much outcome data were missing, whether missingness occurred at baseline or follow-up, or how missing values were handled. The specific analysis population is not reported in the registry record. Completion counts therefore should not be treated as proof that every completer had a usable primary endpoint measurement or that every enrollee was included in the analysis.

In general, a complete-case analysis uses participants with the measurements needed for that analysis, whereas other approaches may use modeling or imputation under explicit assumptions. Each approach relies on assumptions about the missing data. The registry record does not identify an approach or state assumptions about missingness. This limits assessment of whether the reported participant flow could affect the interpretation of an endpoint estimate; the endpoint estimate itself is also not reported.

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 posted safety figures describe one arm, Arm I, with thirty-six participants listed as at risk for serious adverse events and thirty-six listed as at risk for other adverse events. The serious adverse-event count is zero, and the count for other adverse events is fourteen. The death count is zero. These are counts in the registry record; no rates or comparisons are calculated.

The figures are descriptive and do not establish whether an event was caused by vitamin B12. With no comparator group, the record cannot show whether event counts differ from what would occur under another treatment or without the intervention. The registry does not list serious adverse-event terms, and the types, severity, timing, and outcomes of the other adverse events are not reported in the registry record.

For context, the primary endpoint follow-up is described as 90 days (+/- 10 days), but a safety-specific observation period is not reported in the registry record. The figures should therefore be read as the safety counts recorded for the study, not as a complete account of all possible harms or as a comparative safety estimate.

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

The registry record establishes that a single-group study evaluated oral vitamin B12 in women with early-stage breast cancer and aromatase inhibitor-associated musculoskeletal symptoms. It identifies average joint pain percentage change on the BPI-SF as the primary endpoint and gives a baseline-to-follow-up schedule. It also records participant enrollment, withdrawal, and completion counts. These details clarify what the study set out to examine and how the primary symptom measure was framed.

The record does not report the primary endpoint result. It therefore does not show whether average pain increased, decreased, or remained similar, how large any change was, or how precise an estimate might be. The stated expectation of at least 20% improvement is not an observed finding. The absence of the primary estimate and its uncertainty means the registry information cannot establish the size or statistical significance of the result.

Even if a before-and-after change were available, the single-group design would not show what would have happened over the same period without vitamin B12. Changes over time can have several explanations, and a concurrent comparator is not listed. This is a limitation of what the design can answer, not evidence that any specific alternative explanation occurred.

The safety counts likewise describe observations in the study arm, rather than a causal or comparative safety result. The record reports no serious adverse events and fourteen other adverse events, but does not identify the latter’s terms or provide a comparator. These figures do not establish that the intervention caused, prevented, or had no effect on adverse events.

Accordingly, the registry information supports a description of the study question, design, endpoint, and recorded safety counts. It does not support a conclusion about treatment benefit, lack of benefit, or comparative safety. The missing outcome statistics and analysis details leave both the magnitude and precision of the primary result unreported.

14. Why This Trial Matters Statistically

This study raises a statistical question that is common in symptom research: how to describe change in a patient-reported measure over time. The BPI-SF average pain item gives a defined scale and asks about pain over the last 24 hours, while the primary endpoint focuses on percentage change from baseline. Clear specification of the symptom, measurement scale, and follow-up timing helps identify what an analysis is intended to estimate.

The design also illustrates why the estimand matters. A single-group study can examine change among participants receiving an intervention, but a change from baseline is not the same quantity as a treatment effect relative to a control group. Without a concurrent comparator, the study cannot distinguish the intervention’s contribution from other influences on measurements over time. This distinction is essential when interpreting before-and-after findings.

Participant flow is another important part of interpretation. The registry records forty-one enrolled patients, five withdrawals, and thirty-six completions. Those counts tell readers that not all enrolled participants completed the study, but they do not reveal the reasons, endpoint data availability, or the assumptions used to handle missingness. Transparent reporting of those details is needed to judge how representative an analyzed group may be.

The record lists multiple outcomes and analyses, making multiplicity relevant as a general statistical consideration. A prespecified plan can clarify which outcome is primary and how additional analyses will be interpreted. The registry does not report whether adjustment or another strategy was used. Finally, the absence of primary outcome estimates and uncertainty measures illustrates that a study question and design do not alone answer the clinical question: interpretation requires the results and a clear account of how they were analyzed.

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 immediate limitation in the registry record is that the primary endpoint result is not reported. The mean percentage change, standard deviation, confidence interval, and p-value are not reported in the registry record. This prevents assessment of the direction, magnitude, variability, and precision of the primary outcome.

The single-group design has no concurrent comparator. Any baseline-to-follow-up change would therefore be difficult to attribute specifically to the intervention, because the design does not directly account for changes that might occur over time for other reasons. Allocation is listed as NA and masking as NONE; the record does not describe randomization or masking.

Participant information is limited. The primary outcome description gives enrollment, withdrawal, and completion counts, but reasons for withdrawal, demographic or clinical characteristics, and the primary analysis population are not reported in the registry record. Missing-data extent and handling are also not reported. These omissions make it difficult to assess the representativeness of participants with outcome data and the possible effect of missing measurements.

The intervention description identifies oral vitamin B12, but dose, schedule, adherence, and concurrent care are not reported in the registry record. The record lists several secondary outcomes and multiple analyses but does not report their results or explain how multiplicity was handled. Details of the statistical model and outcome calculation are not reported either.

Safety reporting is limited to counts: the registry does not list serious adverse-event terms and does not report the types, timing, or severity of other adverse events. A safety-specific observation period is not reported in the registry record. Together, these limitations constrain both the interpretation of any potential symptom change and the ability to characterize safety from the registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Vitamin B12 for Aromatase Inhibitors Musculoskeletal Symptoms — NCT03069313.
• Registry record last updated 2018-02-01; status last verified 2018-01.
• Results first posted 2018-02-01.
• 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

NCT03069313 is a completed single-group study of oral vitamin B12 for aromatase inhibitor-associated musculoskeletal symptoms in women with early-stage breast cancer. The official title describes a single-arm phase II study; the registry phase entry is NA. Texas Tech University Health Sciences Center, El Paso is listed as sponsor.

The primary endpoint is percentage change in average joint pain on the BPI-SF from baseline to 90 days (+/- 10 days). The registry states that forty-one patients enrolled, five withdrew, and thirty-six completed the study. It does not report the primary endpoint result, its uncertainty, or the analysis approach. The recorded safety figures are zero serious adverse events, fourteen other adverse events, and zero deaths in the study arm.