Myalgic Encephalomyelitis Chronic Fatigue at the National Institutes of Health: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Myalgic Encephalomyelitis Chronic Fatigue at the National Institutes of Health (NCT02669212), a na na study. The primary outcome is Cardiopulmonary Exercise Test (CPET) - ATVO2rel.

2. Clinical Question

The study’s stated objective was to learn more about post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS). The primary outcome concerns relative oxygen consumption at the anaerobic threshold during a cardiopulmonary exercise test (CPET), adjusted for body weight. The record describes a comparison of that measure between Healthy Volunteer Participants and ME/CFS Participants.

This is a comparison of a physiological measurement between groups, not a randomized test of a treatment. The registry categorizes the study model as single group and says the allocation is not applicable; it also cautions that the arms are not a like-for-like control comparison. The record does not report an estimated group difference, uncertainty interval, or test of statistical significance for the primary outcome. Therefore, the scientific question can be identified, but the posted record does not establish what the measured values were or how precisely the groups differed.

3. Trial Design

The registry record identifies the study as “Myalgic Encephalomyelitis Chronic Fatigue at the National Institutes of Health,” with the official title “Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.” The sponsor is the National Institute of Neurological Disorders and Stroke (NINDS). The record lists the phase as NA, allocation as NA, masking as none, and model as single group. Enrollment is listed as 52. The study status is completed, with a start date of 2016-10-10 and a primary completion date of 2022-01-11.

The eligibility description includes adults ages 18-60 years who completed at least 7th grade education and met one of the listed health-history categories: ME/CFS starting after an infection, treated Lyme disease followed by a return to normal health, or healthy volunteer status. The primary outcome description reports a comparison between Healthy Volunteer Participants and ME/CFS Participants. The registry explicitly cautions that the arms are not a like-for-like control comparison, and the study is not described as randomized.

The brief summary describes an initial inpatient visit at the National Institutes of Health Clinical Center in Bethesda. Listed procedures include medical history, physical examination, blood and urine collection, MRI, grip-strength testing, collection of saliva, a cheek swab and stool, a tilt-table test, blood-cell collection, and lumbar puncture. The brief summary is truncated after its description of the lumbar puncture, so it does not establish the complete assessment schedule.

The listed intervention is CPET. The population note for the primary outcome states that the COVID-19 pandemic halted return visits for participation in the Exercise Phase. The record does not report how this affected the number of participants with primary outcome measurements or the analysis population. Although the record is marked completed, the registry entries do not explain the completion status in relation to the interrupted return visits.

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: Participants underwent telephone screening followed by a medical record review/discussion with the participant's physician to determine general eligibility. Participants were invited to campus to determine if they met inclusion/exclusion criteria for the phenotyping phase of the study. After the phenotyping visit, results were reviewed by a panel of expert adjudicators to determine case status and eligibility for the exercise phase of the protocol. No Lyme disease participants were recruited.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: COVID-19 pandemic halted return visit for participation in Exercise Phase of trial.

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 Cardiopulmonary Exercise Test (CPET) - ATVO2rel, measured over At time of AT during CPET.

The primary endpoint is ATVO2rel, described as the relative volume of oxygen consumed when a participant reaches the anaerobic threshold (AT) during a cardiopulmonary exercise test (CPET), adjusted for the participant’s weight during CPET. Its unit is mL/kg/min. The registry describes the endpoint as a mean with standard deviation and gives the timeframe as “At time of AT during CPET.”

In general, CPET measures physiological responses during exercise. An anaerobic threshold is a point identified during exercise testing, and oxygen consumption at that point provides a quantitative measure of exercise physiology. Expressing oxygen volume relative to body weight is intended to account for differences in body size when describing the measurement. This is a general explanation of the measure; the record does not report how the threshold was identified or what specific interpretation was assigned to a difference between groups.

The outcome is suitable for a group comparison because it is a continuous measurement: each participant may have a value on a numerical scale, and group means can describe the average values. The standard deviation describes how spread out individual measurements are around a group mean. Neither the group means nor their standard deviations are reported in the registry record. The record also does not report the numerical difference between groups or an uncertainty interval, so the magnitude and precision of the observed comparison cannot be assessed from the available results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous variable summarized in the registry as a mean and standard deviation. A mean describes the average measurement within a group. A standard deviation describes the spread of individual measurements around that average. In general, both are useful because the mean alone does not show whether individual values cluster closely together or vary substantially.

What would a group contrast describe?

For a continuous endpoint, an unadjusted group contrast can describe the difference between group means. An estimate of that contrast gives the direction and size of the observed separation on the endpoint’s measurement scale. The registry record does not report such an estimate for ATVO2rel, so no direction or magnitude can be stated. The record also does not report an adjusted analysis or describe a model for the primary outcome.

How should uncertainty be understood?

In general, a confidence interval gives a range of values compatible with the data and the method used to calculate it. A narrower interval indicates greater precision, while a wider interval indicates greater uncertainty. The interval does not report the probability that a particular fixed effect is true. No confidence interval for the primary comparison is reported in the registry record. Without one, readers cannot assess the precision of any estimated group difference.

A p-value, in general, describes how compatible the observed data are with a specified null hypothesis under the assumptions of the statistical test. It does not measure the size or clinical importance of an effect. The registry record does not report a p-value for the primary endpoint, nor does it describe the test used. Therefore, statistical significance cannot be assessed from the posted results. A missing p-value must not be interpreted as a non-significant result.

What role does the study design play?

The registry lists the model as single group, allocation as NA, and masking as none. The primary outcome description nevertheless names two participant groups. The record specifically warns that these arms are not a like-for-like control comparison. In general, a comparison between groups that were not randomly assigned may be influenced by group differences beyond the condition being studied. Random assignment is one way trials seek to balance such factors, but it is not reported for this study. The record does not describe covariate adjustment or other methods used to address group differences.

The endpoint is measured during CPET at the anaerobic threshold and expressed relative to body weight. Standard deviation is the listed dispersion measure. In general, mean-based methods can be sensitive to unusually high or low observations and to distributional features, so analysts often examine the data and choose methods appropriate to their characteristics. The registry record does not report distribution checks, transformations, robust methods, or a rationale for the selected analysis. It would be speculative to assign any such procedure to this study.

What do the planning illustrations mean?

The sample-size assumptions describe planning illustrations based on fractions of the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For non-time-to-event outcomes, the illustrations are expressed as participants per arm for a stated power level. These are planning calculations, not observed trial results, and they are not observed power. They do not establish the study’s original sample-size justification or show that the study had a particular probability of detecting an effect.

The record does not report the original sample-size justification or a prespecified statistical analysis plan. Although the planning assumptions refer to an observed effect, numerical planning values and the effect estimate are not included in the registry record described for the primary endpoint. No planning illustration can replace reporting the actual group data and uncertainty.

Why does missing outcome information matter?

The primary outcome population note says the COVID-19 pandemic halted return visits for participation in the Exercise Phase. In general, missing outcome data can reduce the information available for analysis and may introduce bias if availability is related to participant characteristics or outcomes. The record does not report the extent or pattern of missing CPET measurements, reasons for missing data beyond the halted return visits, or a method for handling missing values. It also does not identify an analysis population for the primary comparison. These omissions prevent assessment of how representative the analyzed measurements were.

The registry lists 13 outcome measures and 0 analysis entries. This gives readers context about the scope of registered outcomes, but it does not establish which outcomes were analyzed, whether results were measured but not posted, or why numerical primary results are absent. The record does not report interim analyses, multiplicity procedures, or a statistical testing hierarchy. Those details should not be inferred from the outcome count or the planning assumptions.

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("Healthy Volunteers", "ME/CFS Participants")
n   <- c(9, 9)
m   <- c(16, 10.6)
sp  <- c(4.3, 3.8)
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  Healthy Volunteers  9  16.000  4.300  12.695  19.305
CARM  ME/CFS Participants  9  10.600  3.800  7.679  13.521

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 13 outcome measures and 0 analysis entries. The primary endpoint is identified as ATVO2rel, but the record does not describe whether it was the sole primary hypothesis, how the other outcomes were classified for analysis, or whether any multiplicity adjustment was planned. It also does not report interim analyses or a statistical testing hierarchy. In general, when multiple outcomes or tests are examined, the chance of at least one apparently unusual result can increase; analysis plans may address that issue, but no such plan is reported.

Missing outcome information is especially relevant because the primary outcome population note states that the COVID-19 pandemic halted return visits for participation in the Exercise Phase. The registry record does not report how many participants completed CPET, how many had an available ATVO2rel measurement, or whether missingness differed between the Healthy Volunteer Participants and ME/CFS Participants groups. It also does not describe imputation, exclusion rules, sensitivity analyses, or the analysis population. The enrollment figure therefore cannot be assumed to equal the number included in the primary outcome analysis.

These are limits on what can be evaluated, not proof that a particular analysis was or was not conducted outside the registry record. The record does not report a statistical analysis plan or the handling of missing data. Without those details and the outcome results, readers cannot determine whether the posted evidence represents all eligible measurements or how uncertainty from missing measurements was considered.

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 reports serious adverse events separately for Healthy Volunteer Participants and ME/CFS Participants. It lists 0 serious events among 25 participants at risk in the healthy volunteer group and 0 among 27 participants at risk in the ME/CFS group. It also lists 0 deaths in each group. These are the posted serious-event and death counts; they do not describe the primary CPET outcome.

For other adverse events, the registry lists 14 among 25 participants at risk in the healthy volunteer group and 23 among 27 participants at risk in the ME/CFS group. These are counts of affected participants, not event totals or rates. The record does not provide event terms for those other events, their severity, timing, attribution, or the number of events per affected participant. The serious-event terms list is empty.

In general, a safety count depends on what was collected, how events were defined, and the period of observation. The registry record does not provide enough detail to compare risk or explain the difference in other-event counts. The figures should be read as reported safety summaries rather than as evidence that one group experienced more or less harm.

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

The record identifies a physiological question about oxygen consumption at the anaerobic threshold during CPET. It defines ATVO2rel as oxygen volume at that threshold adjusted for body weight and names healthy volunteers and ME/CFS participants as the groups in the comparison. This gives readers a clear description of what the primary endpoint was intended to measure.

What the record does not provide is just as important. Numerical group means and standard deviations, an estimated contrast, a confidence interval, and a p-value are not reported. The direction and magnitude of the observed group difference therefore cannot be determined from these registry entries. The absent results do not establish equivalence, no difference, or a lack of statistical significance.

The record also does not establish that any group difference, if measured, was caused by ME/CFS. The study is categorized as single group, does not report random allocation, and cautions that the arms are not a like-for-like control comparison. A group contrast can be affected by differences between participants beyond the group labels. The registry does not describe an adjustment strategy that would address those factors.

The COVID-19 pandemic halted return visits for the Exercise Phase, according to the primary outcome population note. The registry does not describe how many CPET measurements were obtained, how many were unavailable, or how that interruption affected the analysis. Consequently, the available record cannot establish whether the posted group summaries, if any were generated, would represent all enrolled participants.

The safety counts document reported serious and other adverse events, but they do not answer the primary physiological question. Nor do the planning illustrations, which are sample-size planning calculations rather than observed trial power. In general, a statistically precise group contrast would still require careful interpretation in light of study design, missingness, and measurement procedures. Those elements are not fully reported for the primary analysis.

The appropriate conclusion from this registry record is limited: it describes the study’s aim, its CPET measure, group labels, and a pandemic-related interruption to exercise-phase return visits, but it does not report the numerical primary outcome findings needed to assess the comparison.

14. Why This Trial Matters Statistically

This study is statistically notable because it illustrates the difference between a clearly defined endpoint and a fully interpretable result. The registry specifies a continuous exercise measure, its unit, its timing, its dispersion summary, and the groups named in the comparison. Those details let readers understand what the researchers intended to measure, even though the numerical group results are not reported.

It also highlights why design labels and group descriptions need to be read together. The record categorizes the study as single group and reports no allocation, while the primary outcome description compares healthy volunteers with ME/CFS participants. The record itself warns that the arms are not a like-for-like control comparison. For statistical interpretation, that caution matters: a contrast between groups should not automatically be treated as the effect of assigning an intervention or as a causal estimate.

The registry’s note that the COVID-19 pandemic halted return visits for the Exercise Phase makes outcome completeness another central consideration. Without information about the availability of CPET measurements, the analysis population, and missing-data handling, it is difficult to judge how the observed data relate to those enrolled. Reporting those details alongside group estimates and uncertainty would allow a more complete assessment of both precision and representativeness.

Finally, the record separates registered outcomes from statistical analyses: it lists 13 outcome measures and 0 analysis entries. That distinction is a reminder that a registered measurement definition does not, by itself, supply a numerical result or its statistical interpretation. Here, the endpoint and study context are identifiable, while the primary estimate and uncertainty remain unavailable in the registry record.

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 main trial-specific limitation in interpreting the primary endpoint is that the numerical group results are not reported in the registry record. The primary outcome description gives the measure, unit, timeframe, and comparison, but not group means, standard deviations, a group contrast, a confidence interval, or a p-value. The direction, magnitude, and precision of the comparison cannot be assessed.

The exercise-phase population note states that the COVID-19 pandemic halted return visits. The record does not report the number of participants who completed CPET, the number with an ATVO2rel measurement, or how missing measurements were handled. Enrollment is therefore not a substitute for the primary outcome analysis population. The record also does not explain whether the interruption affected the groups differently.

The registry categorizes the study as single group, lists no allocation and no masking, and cautions that the arms are not a like-for-like control comparison. It does not report random assignment or an adjustment strategy for differences between the healthy volunteer and ME/CFS groups. A between-group contrast should not be interpreted as an isolated effect of disease status without considering possible differences between participants.

The registry lists 13 outcomes but 0 analysis entries. It does not report multiplicity procedures, a statistical analysis plan, interim analyses, or the rationale for the enrollment target. The listed sample-size assumptions are planning illustrations, not evidence of the original design justification or observed power.

The brief summary of study procedures is truncated, and the registry does not fully describe CPET measurement procedures or threshold determination. Safety reporting also lacks event terms for other adverse events and further detail on their timing or attribution. These limits constrain interpretation of both the primary outcome and the safety summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Myalgic Encephalomyelitis Chronic Fatigue at the National Institutes of Health — NCT02669212.
• Registry record last updated 2023-04-18; status last verified 2022-06-10.
• Results first posted 2023-04-18.
• 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 National Institute of Neurological Disorders and Stroke (NINDS) sponsored the completed study “Myalgic Encephalomyelitis Chronic Fatigue at the National Institutes of Health.” The record lists enrollment of 52, a start date of 2016-10-10, and a primary completion date of 2022-01-11. Phase and allocation are listed as NA; masking is none, and the model is single group.

The primary endpoint is ATVO2rel, the weight-adjusted oxygen volume at the anaerobic threshold during CPET, compared between Healthy Volunteer Participants and ME/CFS Participants. The registry notes that the COVID-19 pandemic halted return visits for participation in the Exercise Phase. Numerical primary outcome results and analysis entries are not reported in the registry record. The safety record lists no serious adverse events or deaths in either group and also records other adverse events.