Comorbidities Associated With Migraine and Patent Foramen Ovale (CAMP): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comorbidities Associated With Migraine and Patent Foramen Ovale (CAMP) (NCT01257880), a registered phase not stated study. The primary outcome is Cerebral Vasomotor Reactivity (VMR).

2. Clinical Question

The broader study description asks whether comorbidities associated with migraine aura differ according to the presence of a large circulatory right-to-left shunt. It mentions possible links between PFO and several health conditions, but those background statements do not establish that PFO causes a condition or that a group difference in this study would be causal.

The registry lists oxygen desaturation index and white matter lesions as secondary outcomes. It does not report their results in the record. The primary endpoint is listed at baseline, so the clinical question concerns a measurement made during a testing period rather than a reported change over follow-up.

3. Trial Design

CAMP is a completed clinical study sponsored by Swedish Medical Center. The registry lists a start date of 2010-01 and a primary completion date of 2011-05, with enrollment of 31. Its stated purpose was to compare the rate of migraine-aura-associated comorbidities between people with and without a large right-to-left shunt. The listed primary outcome, however, is cerebral vasomotor reactivity, a continuous measure recorded at baseline.

The two described groups are “Control (absence of PFO)” and “Large PFO.” The control group consisted of people with migraine aura and no evidence of PFO on transcranial Doppler evaluation; the other group consisted of people with migraine aura and a large PFO assessed by the same method. The registry does not state how participants came to be in either group. It explicitly identifies this as not a randomized comparison and cautions that the arms are not a like-for-like control comparison.

That distinction matters for interpretation. A group comparison in an observational design can describe an association, but group membership may also be related to other characteristics. The record does not provide enough information to judge whether the groups were comparable on measured or unmeasured factors, or whether any adjustment was made.

The primary endpoint is described as the mean percentage change in basilar artery blood flow velocity between hypercapnia and hypocapnia, measured by transcranial Doppler during a single testing period. The record names oxygen desaturation index and white matter lesions as secondary outcomes, and lists seven outcome measures overall. It lists one analysis. The statistical analysis plan, the participant flow into each outcome analysis, and the handling of missing measurements are not reported in the registry record.

The record gives enrollment and safety-group counts, but does not describe recruitment procedures, the setting in which testing was performed, or the timing of outcome assessments beyond the primary endpoint’s baseline timeframe. It also does not report a sample-size justification or an interim-analysis plan. The fact that the study is marked completed establishes its registry status, not whether every planned measurement was obtained or reported.

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: Of 127 potential subjects screened, reasons for exclusion included the following: 22 (17%) chronic migraine or medication overuse headache; 9 (7%) topiramate use; 6 (5%) stroke or multiple sclerosis; 39 (31%) other (declined, low frequency); 12 (9%) small to medium sized PFO; 8 (6%) fetal origins.

Overall 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 Cerebral Vasomotor Reactivity (VMR), measured over Baseline.

Cerebral vasomotor reactivity (VMR) is listed as the primary endpoint. It is a continuous measure expressed as percentage change. The registry defines it using basilar artery blood flow velocity measured by transcranial Doppler: the velocity during hypercapnia is compared with the velocity during hypocapnia, with the baseline velocity used in the calculation. Hypercapnia means increased blood carbon dioxide; hypocapnia means decreased blood carbon dioxide. The measurement is described as occurring during a single testing period at baseline.

The endpoint is used to characterize how cerebral blood flow velocity responds across those carbon-dioxide conditions. A continuous measure can preserve information about the size and direction of observed values, rather than reducing a measurement to a yes-or-no category. In a group comparison, the relevant descriptive quantities would include each group’s mean and variability, followed by an estimate of the difference and its uncertainty. The registry identifies the endpoint as a mean with standard deviation as its dispersion measure, but does not report the group means, standard deviations, or a between-group estimate.

VMR is a physiological measurement, not itself a direct measure of headache burden, stroke, cognition, or another clinical event. The registry’s description of the study rationale discusses possible connections among migraine aura, PFO, and other conditions, but the endpoint alone cannot establish the mechanism behind such connections. Because the primary result is not reported in the registry record, the magnitude, direction, and precision of any group difference cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods matter because the same observed data can support different conclusions depending on the estimand, the analysis choices, and the completeness of reporting. In this record, the endpoint definition and its mean-and-standard-deviation summary are described, but the primary outcome values and inferential analysis are not reported. The following concepts explain how such results are ordinarily read; they do not imply that a particular method was used in CAMP unless the registry states it.

What does a mean describe?

A mean is a summary of the central value of a continuous measurement. For VMR, the registry identifies the mean as the endpoint parameter and standard deviation as the dispersion measure. The standard deviation describes the spread of individual measurements around a group mean. It is not the same as the uncertainty in the estimated mean: uncertainty also depends on how many observations contribute and on the analysis. The registry record does not give the VMR means, standard deviations, or analysis-specific participant counts.

For a comparison, readers generally need the group summaries and an estimate of the contrast between groups. The contrast puts the difference on the endpoint’s scale, while an uncertainty interval indicates how precisely it has been estimated. A narrow interval is generally more informative about the range of plausible contrasts than a wide interval, although interpretation also depends on the study design and measurement quality. No such contrast or interval is reported for the primary endpoint in this registry record.

Why does the design affect interpretation?

Random allocation can, under appropriate conditions, balance measured and unmeasured prognostic factors on average. CAMP is explicitly not described as a randomized comparison; allocation is not stated, and the registry cautions that the groups are not a like-for-like control comparison. This means group differences could reflect factors associated with PFO status as well as differences in the endpoint. Statistical adjustment can address measured factors only when those factors are recorded and appropriately modeled. The record does not report an adjusted analysis or identify adjustment variables.

The design also affects the scope of the question. The groups are defined by transcranial Doppler evaluation, not by assignment to a PFO-related intervention. Thus the intended comparison is between observed groups. General causal language should not be used to convert an association into a treatment effect or a claim about mechanism.

What is over-dispersion?

Over-dispersion is a general statistical issue that arises when observed variability exceeds what a model assumes. It can make standard errors too small if ignored, leading to intervals that are too narrow or tests that appear more decisive than warranted. This concept is especially relevant to count or event models. VMR is described as a continuous measure, and the registry does not report a model or any assessment of over-dispersion for the primary endpoint. It would therefore be inappropriate to claim that over-dispersion was present, absent, or addressed in this study.

How should planning calculations be understood?

The registry’s planning illustration is described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. For this continuous outcome, the planning figures are participants per arm for 80% power or other stated power levels, rather than a count of events. These are planning illustrations, not observed power and not evidence that the original trial was designed with those assumptions.

A planning calculation depends on assumptions about the effect size, variability, allocation, and analysis. If the observed effect is uncertain, basing a future planning illustration on it can carry that uncertainty forward. The registry record does not report the primary outcome summaries needed to assess the observed effect, and does not report the trial’s own sample-size justification. The planning illustration should therefore not be mistaken for evidence about the strength or reliability of the study result.

What do confidence intervals and p-values add?

In general, a confidence interval communicates estimation uncertainty over the scale of an effect. A p-value summarizes how incompatible the observed data are with a particular null hypothesis under a model. Neither is a substitute for the estimated effect, and neither establishes clinical importance. A small p-value does not measure the size of an effect; a larger p-value does not prove equivalence. The registry record does not report a confidence interval or p-value for VMR, so those interpretations cannot be made for CAMP from the posted results.

What can one listed analysis tell readers?

The registry lists one analysis and seven outcome measures. That description does not specify whether one analysis included multiple endpoints, whether secondary outcomes were analyzed separately, or how any multiple-testing issue was handled. Nor does it establish which results were prespecified or reported. The model, test, covariates, missing-data method, and analysis population are not reported in the registry record. Those omissions limit reproducibility and make it impossible to assess whether the posted analysis, if any, follows a prespecified plan.

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("Control (Absence of PFO)", "Large PFO")
n   <- c(12, 19)
m   <- c(89, 97)
sp  <- c(20, 24)
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  Control (Absence of PFO)  12  89.000  20.000  76.293  101.707
CARM  Large PFO  19  97.000  24.000  85.432  108.568

11. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures, identifies VMR as the primary outcome, and names oxygen desaturation index and white matter lesions as secondary outcomes. It also lists one analysis. These entries do not explain how many statistical tests were conducted, whether the analysis covered multiple endpoints, or how outcomes were prioritized in reporting. A multiplicity plan, including any adjustment or hierarchy among outcomes, is not reported in the registry record.

Multiplicity is a general concern when several outcomes or hypotheses are examined: the chance of at least one apparently notable finding can increase as more comparisons are made. This does not mean that every analysis must use the same correction. Interpretation depends on the planned questions, endpoint hierarchy, and analysis strategy, none of which is described in enough detail. The single listed analysis should not be taken to mean that only one hypothesis was tested.

The registry does not report missing-data counts, reasons for missing measurements, or methods for handling missing values. It also does not state the analysis population for VMR or whether all participants with an available measurement were included. The overall enrollment is recorded as 31, while the primary outcome analysis denominator is not reported. Safety-group counts should not be assumed to be the primary analysis counts.

Without this information, readers cannot assess whether missingness could have affected the primary comparison or whether an analysis population was defined in advance. These are reporting gaps, not evidence that missing data occurred or that a particular method was used. Results for the secondary outcomes are also not reported in the registry record.

12. Safety Results

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

Other (non-serious) adverse events

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

The registry lists safety counts separately for “Control (Absence of PFO)” and “Large PFO.” In the control group, 12 were listed as at risk for serious adverse events and 0 as affected; the corresponding other-adverse-event entries are 12 at risk and 0 affected. In the large-PFO group, 19 were listed as at risk for serious adverse events and 0 as affected; the other-adverse-event entries are 19 at risk and 0 affected.

These are registry counts. They do not establish that the risks in the groups are equal or that the risk of an event is absent. Zero recorded events in a group can coexist with uncertainty about the underlying event rate, particularly when the available observation is limited. A comparative safety assessment would also require context about event definitions, follow-up and ascertainment procedures, and the analysis population. Those details are not reported in the registry record.

Deaths are recorded as null for both groups, so a death count is not reported. The record does not provide descriptions of individual adverse events or the criteria used to classify seriousness. The listed safety figures should therefore be read narrowly as the posted event entries, not as a complete evaluation of safety.

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

The CAMP registry record establishes that the study was completed and that its primary outcome was defined as cerebral vasomotor reactivity, measured at baseline by transcranial Doppler. It also describes two observational groups based on PFO assessment and states that the intended comparison concerned migraine-aura-associated comorbidities. These design details identify the question the study set out to address.

The posted record does not report the primary outcome values or an estimate comparing the groups. It therefore does not show whether mean VMR was higher, lower, or similar in the large-PFO group relative to the group without evidence of PFO. No conclusion about the precision or statistical significance of the primary comparison can be made from the available registry entry. The registry also does not report results for the listed secondary outcomes.

Even if a group contrast were available, the nonrandomized design would limit causal interpretation. Group membership was based on PFO assessment, and the registry cautions that the arms are not a like-for-like control comparison. An observed association would not establish that PFO caused a difference in VMR, nor would it establish the mechanism described in the study background.

The absence of a reported result is not a finding of no difference. It is also not evidence of equivalence. Establishing equivalence or ruling out differences would require an appropriate design and a reported estimate with uncertainty evaluated against a prespecified margin. Such a margin and such results are not reported in the registry record.

Likewise, the safety entries of zero adverse events in each group should not be read as proof of no risk. They are counts without the additional context needed to evaluate ascertainment or comparative safety. The strongest defensible reading is limited: the record describes the study question, endpoint, groups, and selected safety entries, but does not provide enough outcome or analysis information to judge the primary comparison.

14. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between a physiological measurement and the broader clinical questions used to motivate a study. VMR is defined as a continuous response in basilar artery blood flow velocity under carbon-dioxide conditions. The broader rationale concerns migraine aura, PFO, and associated conditions. A measurement can help characterize physiology, but it does not by itself establish a clinical mechanism or explain a patient’s symptoms.

The design also illustrates why comparison groups need to be understood before interpreting a difference. Here, the groups are defined by observed PFO status, and the registry says that allocation is not stated and the arms are not a like-for-like control comparison. Such groups can be informative for describing associations, while remaining vulnerable to differences between the people who make up each group. The design label and caveat are therefore central to how any result should be interpreted.

Clear reporting of estimates and uncertainty would be especially important for a continuous outcome. Group means alone would describe the measurements, while an estimated contrast and its uncertainty would show how precisely the comparison was made. Those primary results are not reported in the registry record. This makes the record valuable for identifying the planned endpoint and design, but insufficient for judging the observed association.

The entry also highlights the importance of reporting analysis populations, missing-data handling, and multiplicity plans. The registry identifies seven outcome measures and one analysis, yet does not describe how outcomes or tests were handled analytically. Such details help readers distinguish a prespecified primary question from exploratory findings and assess how robust an interpretation may be.

Finally, the registry’s explicit caution against treating the arms as like-for-like reinforces a general principle: precision does not resolve design limitations. Even a precise association would require cautious interpretation if group differences could reflect factors other than PFO status.

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 for interpreting the trial is that the registry record does not report numerical results for the primary VMR endpoint. Group means, standard deviations, a between-group estimate, and uncertainty measures are not available. Results for the named secondary outcomes are also not reported in the registry record. This prevents assessment of the direction, magnitude, and precision of the study’s outcome comparisons.

The comparison is observational rather than randomized. The record states that allocation is not stated and that the arms are not a like-for-like control comparison. It does not report participant characteristics by group, adjustment variables, or an adjusted analysis. Consequently, the extent to which other differences between groups could influence a contrast cannot be assessed.

The primary endpoint is identified as a baseline measure during a single testing period. The record does not describe repeatability, quality-control procedures, assessor blinding, or details beyond the transcranial Doppler measurement definition. These omissions limit evaluation of measurement reliability and possible measurement-related bias.

The record lists seven outcome measures and one analysis but does not explain the analysis strategy, multiplicity handling, analysis population, or missing-data procedures. It also does not report a sample-size justification for the original study. Although a planning illustration is described, the registry information does not provide the primary outcome summaries required to assess the observed effect on which that illustration is said to be based.

Safety entries are limited to group counts. Adverse-event definitions, ascertainment procedures, and follow-up context are not reported; deaths are null rather than stated as a count. These limitations make the safety entries difficult to interpret beyond their recorded values. Together, these reporting gaps mean the registry record can describe the design and endpoint but cannot support a detailed appraisal of the primary result.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Comorbidities Associated With Migraine and Patent Foramen Ovale (CAMP) — NCT01257880.
• Registry record last updated 2011-09-27; status last verified 2011-09.
• Results first posted 2011-09-21.
• 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

CAMP is a completed study sponsored by Swedish Medical Center, with a start date of 2010-01, primary completion date of 2011-05, and enrollment of 31. It concerns people with migraine aura and compares groups defined by transcranial Doppler assessment of PFO status.

The primary outcome is baseline cerebral vasomotor reactivity, a continuous percentage-change measure of basilar artery blood flow velocity between hypercapnia and hypocapnia. The registry lists oxygen desaturation index and white matter lesions as secondary outcomes.

The record identifies the comparison as nonrandomized, states that allocation is not stated, and cautions that the groups are not a like-for-like control comparison. It does not report the primary outcome results, secondary outcome results, statistical analysis details, missing-data handling, or multiplicity plan. The safety entries record zero serious and zero other adverse events in both groups; deaths are not reported as counts.