LFMS: Initial Trial in Geriatric Bipolar Depression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for LFMS: Initial Trial in Geriatric Bipolar Depression (NCT02707276), a randomized na study. The primary outcome is Change in Montgomery Asberg Depression Rating Scale (MADRS).

2. Clinical Question

The study’s stated primary aim was to assess the efficacy of LFMS for symptoms of depression and anxiety in older adults with bipolar depression. A further stated aim was to assess possible cognitive benefits from regular LFMS treatments. The primary outcome listed in the record is change in MADRS score. However, the outcome description includes multiple visits and comparisons across both a crossover phase and a parallel phase. The record does not provide a single estimate for active versus sham, or the underlying group means and variability needed to interpret a particular comparison.

Consequently, the clinical question is clear at the level of the intended population, intervention, and symptom scale, but the posted record does not establish what the observed treatment contrast was. The enrollment was 16 and the study status is terminated; neither fact supplies the missing outcome estimates or explains why the study ended.

3. Trial Design

The registry describes a randomized, double-masked, parallel study with an enrollment of 16. The phase is listed as not applicable. The intervention arms are active LFMS and sham LFMS, both classified as devices. The listed sponsor is Mclean Hospital. The study started on 2016-09-07, its primary completion is recorded as 2019-06, and its status is terminated. The reason for termination is not reported in the registry record.

The arm descriptions give a more detailed, two-phase account. In Phase 1, participants were assigned to an active-first or sham-first crossover sequence. Each sequence included three 20-minute treatments once per day for three consecutive days during week 1, followed by three treatments of the other condition once per day for three consecutive days during week 3. The listed Phase 1 sequences therefore expose participants to both active and sham LFMS, in opposite orders.

In Phase 2, the descriptions specify parallel active and sham arms. Each arm received five 20-minute treatments once per day for five consecutive days during week 1. The record does not explain how the crossover and parallel phases relate operationally, whether all participants took part in both phases, or how participants were allocated between the phases. It also does not report washout procedures, masking checks, or the method of randomization.

This combination of a general parallel-design designation and phase-specific crossover and parallel descriptions makes the intended structure important to interpretation. The available description indicates the sequences and treatment schedules, but it is not enough to reconstruct the full participant flow or establish which phase produced each reported analysis. Those details 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: Enrolled subjects underwent thorough screening procedures to determine diagnostic status. Two subjects did not meet diagnostic criteria and thus were not assigned to a group. One subject withdrew from the study due to personal reasons before being assigned to a group.

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.

Population: Analysis population is the same as the assignment in the Participant Flow.

6. Primary Endpoint

The registry lists the primary outcome as Change in Montgomery Asberg Depression Rating Scale (MADRS), measured over Phase 1 cross-over: scores at base visit 1 (week 0), visit 5 (week 2), and visit 9 (week 4). Differences are between visits 5-1 and 9-5. Phase 2 parallel: scores at base visit 1 (day 0) and visit 7 (day 10). Differences are between visits 7-1..

The primary endpoint is change in the Montgomery-Asberg Depression Rating Scale (MADRS), a scale used to assess the severity of depressive symptoms. The registry describes it as a 10-item assessment covering core symptoms of depression. Each item is scored from 0, meaning the symptom is not present, to 6, meaning it is severely present. The total score ranges from 0 to 60, with higher scores indicating more depressive symptom endorsement.

A symptom scale offers a structured way to describe severity and change over time. Comparing scores at different visits can show whether measured symptom burden changed during the study period. A treatment comparison is more informative than a change within one group alone because both groups may change over time for reasons not specific to the treatment. That is a general statistical point, not a result from this study.

The registry lists Phase 1 scores at base visit 1, visit 5, and visit 9, with changes defined between visits 5 and 1 and between visits 9 and 5. For Phase 2, it lists scores at base visit 1 and visit 7, with change defined between visits 7 and 1. These are several intervals and time points, rather than one clearly isolated contrast. The record does not state which comparison is the principal estimate for interpreting active versus sham, and it does not provide outcome values, standard deviations, or confidence intervals. Thus, the scale and timing are described, but the magnitude and precision of any primary outcome result are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help turn measurements from participants into an estimate of how outcomes compare between study conditions. For this study, the outcome is continuous: MADRS is recorded as a score, and the registry describes the endpoint using means and standard deviations. General explanations of continuous-outcome methods are useful, but the registry record does not report the actual estimates or a detailed statistical analysis plan.

What does a mean describe?

General: A mean is an average that summarizes the scores in a group. It can provide a compact description of the group’s measured symptom severity at a specified visit or of change over a specified interval. A mean alone does not show how similar or varied the individual scores were. It also does not establish that an observed difference between groups was caused by treatment.

The registry identifies mean and standard deviation as the summary parameter and dispersion measure for the primary outcome. A standard deviation describes the spread of scores around a group mean. Greater spread means that participants’ scores vary more within that group. The record does not report the means or standard deviations at the specified visits, so these summaries cannot be interpreted for this trial.

What does a treatment contrast represent?

General: A treatment contrast compares outcomes under active treatment with outcomes under a comparator. For a continuous endpoint, the contrast could be expressed using group means or mean changes, depending on the analysis. A clear contrast needs a defined population, endpoint, time point, and comparison. In this study, the outcome description includes more than one phase and more than one interval. The registry does not identify one reported contrast or provide values for any of them.

Change scores compare a participant’s or group’s outcome at a later visit with a starting visit. They can describe change over the defined interval, but their interpretation depends on the visit schedule and the comparison being made. The Phase 1 descriptions specify changes between visits 5 and 1 and between visits 9 and 5. The Phase 2 description specifies change between visits 7 and 1. These intervals do not represent one interchangeable estimate. The record does not explain how the multiple intervals were handled in the primary analysis.

How should uncertainty be understood?

General: A confidence interval is a range of values compatible with the data and the statistical model at a stated confidence level. It communicates the precision of an estimate: narrower intervals indicate greater precision, while wider intervals indicate greater uncertainty. It is not a guarantee that the true effect lies within that particular interval. No confidence interval for the MADRS comparison is reported in the registry record, so the precision of the primary outcome estimate cannot be assessed.

A p-value, when reported, describes how compatible the observed data are with a specified null hypothesis under the analysis assumptions. It does not state the probability that a treatment works, nor does it convey the size or clinical importance of an effect. No primary outcome p-value is reported. A p-value alone would also be insufficient to understand the result without an estimate and its uncertainty.

Why can multiple comparisons matter?

General: When an analysis examines several outcomes, time points, or treatment contrasts, the chance of finding an apparently notable result somewhere among them can increase if each is tested separately. Statistical methods may address this through a prespecified primary comparison or an adjustment for multiple testing. The registry record describes multiple time points and intervals, and it lists 3 outcome measures and 6 analyses. It does not report whether the analyses were prespecified in a protocol, whether multiplicity adjustments were used, or how any adjusted results should be interpreted.

The record explicitly notes that the primary outcome has several categories or time points and is not reduced to one comparison. That limits the ability to identify a single primary estimate from the posted outcome description. The existence of several analyses does not establish that every analysis was treated as confirmatory, nor does it establish that an adjustment was or was not performed. Those details are not reported in the registry record.

What do the design labels contribute?

General: Random allocation is intended to reduce systematic differences between groups at the point of assignment. Double masking is intended to limit the influence of knowledge about assignment. A parallel design compares groups assigned to different conditions, whereas a crossover design has participants receive more than one condition in sequence. These design concepts have different implications for analysis: a crossover comparison may depend on within-participant measurements and treatment order, while a parallel comparison depends on between-group measurements.

The registry’s general design fields describe randomized, double-masked, parallel allocation, while its arm descriptions include a crossover Phase 1 and parallel Phase 2. The record does not provide enough detail to determine the full analysis model, account for treatment order, describe any period or carryover effects, or establish how phases were combined or kept separate. These methods should not be inferred from the schedule alone.

What can planning calculations tell readers?

General: Sample-size planning illustrations estimate how many participants per arm would be needed under stated assumptions to detect an effect at a chosen power and significance level. Such illustrations depend on assumptions about the effect size and outcome variability, among other factors. They are not observed power, which is not a useful substitute for describing the results after a study has been conducted.

The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between arms, a normal approximation, and effects set as stated fractions of the observed effect. They specify participants per arm for non-time-to-event calculations. The numerical planning values and the observed effect are not reported in the record information. The registry also does not report the trial’s own sample-size justification. The planning framework therefore cannot establish whether the study enrollment was adequate for a particular target effect.

In short, the listed statistical summaries and design concepts indicate what could be used to describe and compare continuous scores. But without the outcome estimates, uncertainty measures, analysis population, and detailed analysis plan, the posted record does not permit a full statistical appraisal of the primary comparison.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome description covers several visits and change intervals: two in the crossover phase and one in the parallel phase. The record also lists 3 outcome measures and 6 analyses. It explicitly indicates that the primary outcome has several categories or time points and is not reduced to one comparison. It does not report which contrast was designated as the primary inferential test, whether comparisons were prioritized, or whether any adjustment for multiple testing was used. As a result, readers cannot determine from the registry record how the different time points and analyses were intended to contribute to a single confirmatory conclusion.

The record does not report an analysis population definition, such as which participants were included in each outcome analysis or how participants with incomplete measurements were handled. It does not report missing-data counts for MADRS, reasons for missing measurements, imputation procedures, or sensitivity analyses. The safety denominators do not resolve those omissions because the record does not explain how they relate to enrollment or to the outcome-analysis populations.

These gaps matter because analysis choices can affect both the estimate and its uncertainty. General: excluding participants with unavailable measurements, using a model to incorporate incomplete repeated measurements, or imputing values involve different assumptions. No particular approach can be attributed to this trial based on the registry record. The methods for handling repeated observations, phase-specific measurements, and incomplete data are not reported in the registry record.

The stated planning assumptions do not fill these gaps. They describe an illustrative calculation framework but do not state the study’s own sample-size justification or its analysis plan. The record does not report interim analyses, stopping rules, or a prespecified multiplicity strategy. Their presence or absence should not be inferred.

11. 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 safety record lists no serious adverse events in either group: 0 among 6 participants at risk in the active LFMS group and 0 among 7 participants at risk in the sham LFMS group. It lists 0 deaths in both groups. For other adverse events, the record reports 2 among 6 participants at risk in the active group and 2 among 7 participants at risk in the sham group.

These are counts alongside the stated numbers at risk. They describe the recorded events in those groups; they do not by themselves establish whether the groups differ in safety. With no event descriptions or timing details in the record, the nature and severity of the other adverse events cannot be characterized. The registry lists no top serious adverse event terms.

The safety denominators are not the same as the overall enrollment of 16, and the record does not explain the difference. It does not report whether the denominators reflect treatment exposure, available safety follow-up, or another rule. They should not be interpreted as the number randomized to each group without further information.

General: Small event counts provide limited information about the range of possible event frequencies, particularly when no additional detail or uncertainty interval is reported. The safety listing is a descriptive account, not a basis for concluding that either treatment is safe or unsafe. The record’s termination status also does not explain whether safety findings influenced the study’s end.

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

The record establishes that a randomized, double-masked study of active and sham LFMS was registered for older adults with bipolar depression. It describes MADRS change as the primary outcome and gives treatment schedules for crossover and parallel phases. It also reports enrollment of 16 and a terminated status. These registry entries characterize the study’s scope and structure, but they are not outcome evidence.

The record does not report the primary MADRS results. There are no posted group means, change estimates, standard deviations, treatment contrasts, confidence intervals, or primary outcome p-values in the available information. Therefore, the direction, magnitude, and precision of the treatment comparison cannot be established. No conclusion about whether active LFMS changed depressive symptom scores relative to sham can be drawn from the reported outcome information.

The record’s stated aims also include anxiety symptoms and possible cognitive benefits. It does not report results for those aims in the information. Nor does it explain the reason for termination. The study status cannot be used as a substitute for a result or as an explanation of why the study ended.

General: A clinical trial estimate is most informative when readers can see the contrast being estimated, the uncertainty around it, and the population and time point to which it applies. A result from a small study can be imprecise, but no estimate is reported to assess precision. Enrollment alone cannot establish how informative the study’s results would be.

The safety record gives counts of serious and other adverse events, with stated group denominators, but does not provide event details or explain the denominators. Those counts should be read descriptively. They do not establish comparative safety.

In sum, the registry record documents the trial design, outcome definition, treatment schedules, and limited safety counts. It does not provide the primary efficacy findings or enough analysis detail to reconstruct them. The appropriate interpretation is therefore a description of what was planned and recorded, with the treatment effect remaining unquantified.

13. Why This Trial Matters Statistically

This study raises several statistical issues that are important when interpreting clinical research. First, the registry’s general design fields identify a randomized, double-masked, parallel study, while its arm descriptions include both crossover and parallel phases. The treatment schedules are described, but the record does not explain how the phases fit together or how their data were analyzed. A clear link between design, participant flow, and analysis is needed to understand what a treatment estimate represents.

Second, the primary outcome involves several visits and intervals. The record states that the outcome is not reduced to one comparison. Multiple time points can describe the course of measured symptoms, but they also make it important to identify the primary contrast and explain how other comparisons were handled. That information is not reported in the registry record.

Third, the registry describes a mean and standard deviation approach for a continuous symptom score, yet the outcome values and uncertainty estimates are not reported in the information available for interpretation. A statistical method is only part of the evidence: readers also need the estimate, its precision, and the analysis population. Without these, the treatment comparison cannot be quantified.

Fourth, the enrollment was 16, and the study is marked terminated. The reason for termination, sample-size justification, and detailed analysis plan are not reported. Planning illustrations based on an observed effect do not establish the trial’s original design assumptions and should not be confused with observed power.

Finally, the safety record presents event counts with group-specific denominators that do not match the overall enrollment, without explaining the relationship. Clear denominators and participant-flow information are essential for interpreting both benefit and safety results. These reporting issues do not determine what the study found; they limit what can be concluded from the registry record.

14. 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 limitation for interpreting this trial is that the registry record does not report the primary outcome results. Without MADRS estimates, variability, treatment contrasts, or confidence intervals, the magnitude and precision of the comparison cannot be evaluated. The outcome description contains several time points and intervals, and the record does not identify one reported estimate as the principal comparison.

The design description is also incomplete for reconstructing the analysis. The general fields describe a randomized, double-masked, parallel study, while the arm descriptions specify a crossover Phase 1 and a parallel Phase 2. The record does not explain whether participants entered both phases, how allocation worked across phases, or how the phase-specific data were analyzed. It also does not report washout procedures or how treatment order was addressed.

Enrollment was 16, but participant flow and outcome-analysis denominators are not reported. The safety record lists 6 participants at risk for active LFMS and 7 for sham LFMS; the relationship between those figures and enrollment is not explained. Missing outcome data, analysis populations, and procedures for handling incomplete measurements are not reported in the registry record.

The record lists 3 outcome measures and 6 analyses and notes multiple primary-outcome time points. It does not report a prespecified multiplicity approach, an interim-analysis plan, or the study’s sample-size justification. The study is terminated, but the reason is not reported. These are limitations of the information available for assessing the study; they do not establish what the investigators did or why the study ended.

Finally, the adverse-event listing offers counts but not event descriptions or additional context. It supports only a limited descriptive reading of the safety record and does not allow a detailed comparison between groups.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: LFMS: Initial Trial in Geriatric Bipolar Depression — NCT02707276.
• Registry record last updated 2022-03-02; status last verified 2022-01.
• Results first posted 2022-03-02.
• 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.

18. Record Summary

The registry describes a randomized, double-masked study of active versus sham low field magnetic stimulation for older adults with bipolar depression. Enrollment was 16. The general design fields specify a parallel model, while the arm descriptions include a crossover Phase 1 and parallel Phase 2. The primary outcome is change in MADRS score across several listed visits and intervals.

The study started on 2016-09-07, has a primary completion date of 2019-06, and is listed as terminated. Mclean Hospital is the sponsor. The reason for termination is not reported in the registry record. The record does not report the primary outcome results, analysis populations, missing-data handling, multiplicity procedures, or sample-size justification. Safety listings report 0 serious adverse events and 0 deaths in both groups, with 2 other adverse events in each group; the denominators are 6 for active LFMS and 7 for sham LFMS.