A Study of L-DOPA for Depression and Slowing in Older Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of L-DOPA for Depression and Slowing in Older Adults (NCT02744391), a na phase 4 study. The primary outcome is Hamilton Rating Scale for Depression (24 Item).

2. Clinical Question

3. Trial Design

This was a Phase 4, completed, single-group study sponsored by New York State Psychiatric Institute. The registry record gives a start date of 2016-08-24 and a primary completion date of 2018-09-14. Enrollment was 47. The study included patients with major depressive disorder, dysthymia, depression not otherwise specified, decreased processing speed, and decreased gait speed.

The intervention was levodopa. The arm description says that participants would receive titration of L-DOPA from 150 mg to 450 mg. The record does not state the titration schedule, duration of treatment, or how dose changes were made. The model is single group, allocation is NA, and masking is none. There is no control group in the design information, and the study is not a randomized comparison.

The main endpoint was the mean on the 24-item Hamilton Rating Scale for Depression at Week 3. The record also lists measures of processing speed, including the Digit Symbol Substitution Test, Pattern Comparison, and Letter Comparison, as well as single-task gait speed. It reports 19 outcome measures overall but does not provide a complete account of the analysis plan or results for those measures.

The registry states that 36 patients were analyzed according to the intent-to-treat analysis. It does not explain the operational definition of that analysis or how participants without endpoint data, if any, were handled. Although the registry status is completed, completion does not itself indicate that outcome estimates were reported. Numerical results for the primary endpoint 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 47 patients were enrolled and 36 patients were analyzed according to the intent to treat analysis.

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 Hamilton Rating Scale for Depression (24 Item), measured over Week 3.

The primary endpoint was the mean score on the 24-item Hamilton Rating Scale for Depression (HRSD) at Week 3. The HRSD is a questionnaire used to assess depressive symptoms and to guide evaluation of recovery. The registry describes a total score range of 0-74, not including the atypical symptoms sub-scale. It states that a score of 16 or above is typically considered to indicate depressive symptoms and that higher scores indicate greater severity.

As a continuous measure, the score can represent symptom severity across a range rather than only classifying a participant as above or below a threshold. A group mean describes the average score for the participants included in an analysis. Its interpretation depends on knowing which participants contributed data, the time point, and whether the value is a follow-up score or a change from an earlier measurement.

The registry identifies Week 3 as the timeframe, but does not report a Week 3 mean, standard deviation, baseline score, change estimate, or confidence interval. It therefore does not show the size or precision of any observed change in depressive symptoms. The endpoint’s clinical purpose is described, but its numerical result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a continuous measure summarized by a mean and standard deviation. These statistics answer different descriptive questions. The mean is the average score among the participants included in an analysis. The standard deviation describes how dispersed individual scores are around that average. In general, a standard deviation is not a measure of how precisely the mean has been estimated; precision depends on the amount of information and the variability in the data.

What would a mean estimate show?

For this study, a Week 3 mean HRSD score would describe the average depressive symptom score at that time point for the analyzed participants. The scale description says that higher scores indicate greater severity. A mean by itself would not show the range of individual experiences, and a follow-up mean alone would not establish how much scores changed from baseline. A change estimate requires a defined reference measurement and a stated method for comparing measurements. Those numerical estimates and details are not reported in the registry record.

How should uncertainty be understood?

In general, a confidence interval gives a range of values compatible with the data under the statistical method used. Its width communicates uncertainty in an estimate: a wider interval indicates less precision than a narrower interval. It does not guarantee that the true value lies in the interval, nor does it resolve design limitations such as the absence of a control group. No confidence interval for the primary outcome is reported in the registry record, so the precision of any endpoint estimate cannot be assessed from the record.

A p-value, in general, measures how unusual data would be under a specified statistical model and null hypothesis. It is not a measure of the size or clinical importance of an effect. A p-value also depends on the analysis choices and assumptions. No primary-outcome p-value or statistical test is reported in the registry information. Consequently, there is no reported inferential result to interpret, and no basis for describing the endpoint as statistically significant or not statistically significant.

What does a single-group design permit?

The study model is listed as single group, with allocation NA and masking none. There is no randomized control group in the record. As a general statistical principle, measurements in one group can describe that group, but a before-and-after difference does not by itself isolate the effect of an intervention. A control group can help account for changes that might also occur without the intervention; a single-group design cannot make that direct comparison. The registry does not report whether an analysis of change was performed.

How do the planning assumptions fit?

The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect. Those are planning assumptions, not descriptions of the trial’s single-group design. The record also cautions that such illustrations are not the trial’s own design. Since this study has no randomized comparison and the numerical observed effect is not reported, those assumptions cannot be treated as evidence of the study’s achieved power or as an analysis of its results. Sample-size planning illustrations are not observed power.

In general, over-dispersion means that observed variability is greater than a statistical model assumes. When a model does not account for excess variability, standard errors can be too small and uncertainty can be understated. The registry information does not report a model for over-dispersion, or any fitted inferential model for the primary endpoint, so no claim can be made that this issue arose in this study.

What can the analysis count establish?

The registry reports 47 enrolled patients and 36 analyzed according to the intent-to-treat analysis. The label indicates the type of analysis claimed, but the record does not define which participants were included or detail how missing outcome values were handled. In general, an analysis population and missing-data method affect what an estimate represents. Without the outcome data and those method details, the reported participant counts cannot be used to reconstruct an endpoint result or its uncertainty.

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("L-DOPA")
n   <- c(36)
m   <- c(10.94)
sp  <- c(6.87)
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  L-DOPA  36  10.940  6.870  8.616  13.264

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures and gives zero analyses. It names the HRSD as the primary outcome, with secondary measures including processing-speed tests and single-task gait speed. However, it does not report an analysis plan that explains how the primary and secondary outcomes were handled, which time points were analyzed, or whether any adjustment for multiple testing was planned or performed.

In general, multiplicity arises when several hypotheses or outcomes are examined. If each is evaluated separately without an appropriate strategy, the chance of at least one apparently unusual result due to random variation can increase. Methods for addressing multiplicity can include prespecifying a primary analysis or adjusting the interpretation of multiple tests. The registry information does not state whether any such method was used, so no conclusion about the multiplicity of the reported analyses is possible.

The registry says that 47 patients were enrolled and that 36 were analyzed according to the intent-to-treat analysis. It does not state how the analysis population was operationalized, whether all enrolled participants had Week 3 HRSD measurements, or how missing values were handled. It also does not report the number of participants contributing data to each outcome. These details are important because an estimate based on observed data can depend on who has measurements and on the assumptions used for missing observations.

The study is listed as single group, with allocation NA. Thus, the intent-to-treat label does not establish the presence of randomized treatment assignments. The record’s description of the analysis population and missing-data approach is not reported in the registry record beyond the count and label given.

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 5% reporting threshold.

The registry’s safety fields list 47 participants at risk in the L-DOPA group. The fields record zero participants with a serious adverse event and zero participants with another adverse event, alongside one death. No serious adverse event terms are listed. These are registry counts; they do not describe the timing, circumstances, or cause of the death.

A count of zero in a reported field should be read narrowly: the registry records zero affected participants for that field. It does not establish why the count is zero or whether all possible events were captured in the information available. The death count is a separate entry and must not be interpreted as evidence that the intervention caused the death. The record does not report a causal assessment.

There is no comparator group, so these counts cannot be used to estimate a relative difference in adverse events between treatments. The record also does not provide detailed event narratives or a comparative safety analysis. The figures describe what is recorded for this group, not a conclusion about treatment safety.

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

The registry record establishes that a completed, single-group study enrolled 47 patients and evaluated L-DOPA in the context of depression and slowing in older adults. It identifies the primary outcome as the mean score on the 24-item HRSD at Week 3 and reports that 36 patients were analyzed according to the intent-to-treat analysis. It also lists cognitive and gait measures and provides selected safety counts.

What the record does not establish is the primary outcome result. No Week 3 mean, change from baseline, standard deviation, confidence interval, or p-value is reported. Without those results, the direction, magnitude, and precision of any observed difference over time cannot be described. The participant counts do not substitute for outcome estimates.

Even if within-group outcome estimates were available, the single-group design would not offer a randomized comparison. General changes over time could have explanations other than the intervention, and the design does not provide a control group to assess those alternatives directly. The registry information therefore cannot establish a comparative treatment effect.

The stated hypothesis links dopamine functioning, cognitive and motor slowing, and depressive symptoms. That is the study’s rationale, not a reported finding. The registry does not report results that would establish whether the listed outcomes changed together or whether any change was attributable to L-DOPA. Likewise, the safety counts do not establish causality or comparative risk. The record supports a description of the study and its reported counts, but not a conclusion that treatment did or did not improve depressive symptoms.

14. Why This Trial Matters Statistically

This study illustrates why design and outcome reporting have to be considered together. The primary measure is clearly identified as the mean Week 3 HRSD score, and the record describes how scores are interpreted. Yet the numerical endpoint result is not reported. Naming an outcome tells readers what was intended to be measured; it does not show what the data demonstrated or how precise an estimate was.

The single-group design is also central to statistical interpretation. Without a control group, the study can describe outcomes among participants receiving L-DOPA, but it cannot make the randomized like-for-like comparison used to distinguish an intervention effect from other changes over time. This is an issue of what the design can support, rather than a judgment about the quality of the intervention.

The record reports 19 outcome measures and zero analyses, while identifying several cognitive and gait measures in addition to the primary depression measure. This makes clear why readers need information about the planned analysis hierarchy, multiplicity, and outcome-specific results. In general, evaluating multiple measures requires care in deciding which findings are confirmatory and how uncertainty is interpreted. Those analysis details are not reported in the registry record.

Finally, the enrollment and analysis counts and the safety entries are not substitutes for outcome estimates. Transparent reporting of endpoint values, uncertainty, missing-data handling, and the analysis population would help readers judge what the study observed. The available record is statistically informative about design constraints and reporting gaps, but it does not provide the primary result.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most direct limitation for interpreting this study is that the registry record does not report numerical results for the primary endpoint. It identifies the HRSD mean at Week 3 but gives no endpoint mean, baseline score, change estimate, standard deviation, confidence interval, or p-value. The size, direction, and precision of the primary outcome therefore cannot be evaluated.

The single-group model, allocation listed as NA, and lack of masking mean that the record does not describe a randomized, controlled comparison. This limits causal interpretation and prevents direct comparison of outcomes between treatment groups. The intervention description states a titration range from 150 mg to 450 mg, but the titration schedule and individual exposure are not reported.

The registry reports that 47 patients were enrolled and 36 were analyzed according to the intent-to-treat analysis, but does not explain the analysis population in detail or state how missing endpoint data were handled. It also does not give participant counts contributing to each outcome. These omissions limit assessment of how the analyzed participants relate to those enrolled.

The record lists 19 outcome measures and zero analyses but does not describe a statistical analysis plan, multiplicity method, or results for the secondary measures. It does not report whether analyses were adjusted or whether sensitivity analyses were conducted. Those details are not reported in the registry record and should not be inferred from the study’s stated aims.

Safety information is limited to the recorded group counts and does not include a causal assessment of the death or a control group for comparison. Together, these limitations mean that the registry supports description of the study design and selected counts, but not a determination of efficacy, comparative safety, or the robustness of an estimated effect.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of L-DOPA for Depression and Slowing in Older Adults — NCT02744391.
• Registry record last updated 2023-06-13; status last verified 2023-05.
• Results first posted 2019-07-05.
• 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

NCT02744391 is a completed Phase 4, single-group study sponsored by New York State Psychiatric Institute. It enrolled 47 patients and evaluated levodopa titrated from 150 mg to 450 mg. Allocation is listed as NA and masking as none; no control group is described.

The primary outcome was the mean score on the 24-item Hamilton Rating Scale for Depression at Week 3. The registry states that 36 patients were analyzed according to the intent-to-treat analysis. It lists 19 outcome measures and zero analyses, but numerical primary outcome results are not reported in the registry record. Safety fields list 47 at risk, zero with a serious adverse event, zero with another adverse event, and one death; no causal assessment is provided.