This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Optimizing the Effectiveness of Selective Serotonin Reuptake Inhibitors (SSRIs) in Treatment-Resistant Depression (NCT00093847), a randomized phase 2 study. The primary outcome is Hamilton Depression Rating Scale Remission Rates.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00093847 |
| Phase | Phase 2 |
| Condition | Depression |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 73 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
People with depression who had not responded to antidepressant treatment alone, as described in the registry summary. Detailed eligibility criteria and baseline characteristics are not reported in the registry record.
Intervention
Adjunct oral S-adenosyl methionine (SAMe) tosylate, listed at 800mg PO BiD.
Comparator
Oral adjunct placebo. The arm description identifies the placebo as a pill taken twice daily.
Primary question
At Week 6, what proportion of participants in each arm met the registry's definition of remission on the Hamilton Depression Rating Scale 17 item (HDRS17)?
The study asks whether adding SAMe to existing antidepressant treatment is associated with a different observed remission proportion than adding placebo for people described as having treatment-resistant depression. The registered primary endpoint is a categorical outcome: a participant is counted as a remitter if the final HDRS17 score is 7 or less. The registry reports the proportions for the SAMe and placebo arms as 46.1% and 17.6%, respectively.
This question is narrower than whether symptoms improved by any amount. It focuses on whether participants crossed the stated remission threshold at the registered assessment time. The record does not report the eligibility details, the antidepressant regimens participants were taking, or other clinical characteristics needed to describe the enrolled population more fully. It also does not report a statistical comparison estimate with a confidence interval or p-value. The percentages therefore describe the posted results, while the precision and inferential strength of the contrast are not quantified in the registry record.
3. Trial Design
The registry identifies this as a phase 2, randomized, double-masked, parallel-group trial sponsored by Massachusetts General Hospital. It is listed as completed, with enrollment of 73. The recorded start date is 2004-05, and primary completion is recorded as 2009-02. The condition is depression, and the study title and summary specify treatment-resistant depression and augmentation of antidepressant treatment.
Participants were assigned to adjunct oral SAMe tosylate or oral adjunct placebo. The registered arm descriptions identify SAMe at 800mg PO BiD and a placebo pill taken twice daily. The reported arm sizes are 39 for SAMe and 34 for placebo. The registry identifies the outcome population as ITT LOCF, but it does not provide a participant flow account or explain how this analysis population was assembled.
In general, randomization uses an assignment process intended to limit systematic differences between groups, while masking is intended to reduce the influence of treatment knowledge on trial conduct or assessment. The registry labels the study randomized and double-masked but does not describe the allocation sequence, concealment procedures, who was masked, or how masking was maintained. A parallel design means the registered arms are compared as separate groups rather than as a planned sequence of treatments for each participant.
The registry record does not report the sample-size justification, a protocol-level statistical analysis plan, interim analyses, or details of treatment adherence and follow-up. Those omissions limit what can be inferred about design decisions beyond the design labels, arms, enrollment, and dates that are recorded.
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: This was a randomzized (1:1) double-blind, placebo-controlled adjunct study of oral SAMe tosylate (target doses of 800mg PO BiD) to standard SSRI and SNRI antidepressants for patients with MDD.
Overall Study
| Stage | Adjunct Oral SAMe Tosylate 800mg PO BiD | Oral Adjunct Placebo |
|---|---|---|
| STARTED | 39 | 34 |
| COMPLETED | 31 | 24 |
| NOT COMPLETED | 8 | 10 |
Analysis population for the primary outcome, as defined in the registry: ITT LOCF
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.
| Characteristic | Unit | Adjunct Oral SAMe Tosylate 800mg PO BiD | Oral Adjunct Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 39 | 34 | 73 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 33 | 32 | 65 |
| Age, Categorical: >=65 years | Participants | 6 | 2 | 8 |
| Age, Continuous | years | 51.4 (SD 14.1) | 48.5 (SD 11.3) | 50.0 (SD 12.9) |
| Sex: Female, Male: Female | Participants | 21 | 23 | 44 |
| Sex: Female, Male: Male | Participants | 18 | 11 | 29 |
| Region of Enrollment: United States | participants | 39 | 34 | 73 |
6. Primary Endpoint
The registry lists the primary outcome as Hamilton Depression Rating Scale Remission Rates, measured over Measured at Week 6.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Percentage of Remitters HDRS17 |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the percentage of remitters on the Hamilton Depression Rating Scale 17 item (HDRS17), measured at Week 6. The registry defines remission as a final HDRS17 score of 7 or less and reports the endpoint for the intention-to-treat, last-observation-carried-forward population (ITT LOCF). The posted percentages are 46.1% for adjunct SAMe and 17.6% for adjunct placebo.
The HDRS17 is a symptom-rating scale, and the endpoint converts the final score into a yes-or-no classification based on the registered cutoff. In general, a threshold-based outcome can be easier to interpret as the proportion reaching a stated clinical state than as a change in the scale's units. That simplification also means information about differences among participants' scores is not represented in the remission percentage. The registry does not give the underlying score distributions or the number of remitters in each arm.
Remission is used as the primary endpoint in this record because the registered question concerns reaching a specified symptom-score threshold by the assessment time, not merely any change from baseline. The registry does not report a rationale for choosing this endpoint or cutoff, nor does it provide other assessment times for the primary result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary result is a remission proportion of 46.1% in the adjunct SAMe arm and 17.6% in the adjunct placebo arm at Week 6. These are descriptive percentages for the registered ITT LOCF population. They indicate how often the endpoint threshold was met in each arm as reported by the registry; on their own, they do not quantify the uncertainty around the difference or establish what caused any observed contrast.
The registry record does not include a confidence interval, p-value, adjusted effect estimate, or analysis output for the primary endpoint. Without such information, the precision of the comparison cannot be assessed from the posted primary result. The arm sizes are 39 and 34, but sample size alone does not provide a substitute for an interval estimate. Counts of remitters are also not reported, so the percentages cannot be checked against exact outcome counts from the record.
In general, a confidence interval describes a range of values compatible with the data and the assumptions of the statistical method. Its width is relevant because an estimate can be uncertain even when the point estimates differ. A p-value, also in general, evaluates how compatible data are with a specified null model; it does not give the probability that a treatment is effective or establish clinical importance. Neither type of inferential result is posted for this endpoint in the registry record.
The record lists the outcome population as ITT LOCF. This identifies the approach used for the posted result at a broad level, but implementation details are not reported. In particular, the number of participants with missing Week 6 measurements, the timing of their last available observations, and the handling of withdrawals are not reported in the registry record. Those details matter when interpreting an endpoint that depends on a final score and uses carried-forward observations.
The registry lists HDRS17 Responders as a secondary outcome, but no secondary numerical result is included in the registry record recorded for this trial. No multiplicity strategy is reported. The record also lists zero analysis entries, so no model specification or test associated with the remission percentages is available in the registry record. Consequently, the most defensible reading is descriptive: the registry reports different observed remission percentages across the two assigned arms, with uncertainty, analysis details, and the secondary result not reported.
Planning calculations based on an observed effect are illustrations of sample sizes under stated assumptions, not observed power and not additional evidence about the trial result. The stated illustration assumptions include a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect to detect defined as a fraction of the observed effect. These assumptions do not establish the trial's own design rationale, which is not reported in the registry record.
9. Statistical Methods Explained
The design labels describe a randomized, double-masked, parallel trial. In general, random assignment is intended to make treatment groups comparable with respect to both measured and unmeasured characteristics, on average across repeated trials. It does not guarantee that every characteristic is balanced in a particular trial. The registry record does not describe the randomization sequence, stratification, allocation concealment, or baseline balance, so those details cannot be assessed from the posted record.
Double masking generally means that more than one group involved in the trial is kept unaware of assigned treatment. Masking can reduce the opportunity for expectations to influence participant reports, clinician behavior, or outcome assessment. The record does not identify which people were masked or describe checks for whether masking was successful. The parallel-group label indicates separate treatment groups; it does not itself specify how the primary endpoint was statistically compared.
The primary measure is a proportion: the share of the analysis population classified as remitters using the stated HDRS17 cutoff at Week 6. The posted arm values are 46.1% and 17.6%. A proportion condenses participant outcomes into the frequency meeting a criterion. In general, this is useful when the clinical question is about reaching a defined state, but it does not show how close non-remitters were to the threshold or how far remitters were below it. The registry does not report the score distributions, exact remitter counts, or a treatment-effect estimate for this endpoint.
To quantify a comparison between proportions, an analysis can estimate a difference or another contrast and report uncertainty around that estimate. The method should reflect the outcome, design, and analysis population. The registry record does not report which comparison method was used, whether the estimate was adjusted for baseline variables, or whether any assumptions were checked. It also does not report a confidence interval or p-value. No particular model or test should therefore be attributed to the posted percentages.
The record labels the analysis population ITT LOCF. In general, intention-to-treat analysis aims to analyze participants according to their randomized assignment, while last observation carried forward uses a participant's most recent available measurement in place of a missing later measurement. The registry does not describe the exact implementation of ITT LOCF in this trial, including whether all randomized participants contributed to the endpoint or what rules applied to participants without an earlier measurement.
Last observation carried forward is an imputation method, not an observed Week 6 measurement. In general, it can make an analysis possible when follow-up values are missing, but it relies on assumptions about how the unobserved outcome relates to the last recorded one. Those assumptions can be implausible if symptoms would have changed after the last measurement. The record does not provide the missing-data count, reasons for missingness, timing of last observations, or sensitivity analyses, so the impact of this method on the reported proportions cannot be evaluated.
The trial is listed as phase 2. That label describes the registered development phase, but it does not reveal the statistical objectives or design rationale. The sample-size justification, target power, planned effect size, and analysis plan are not reported in the registry record. General explanations of trial design should not be mistaken for details of this protocol.
The record lists two outcome measures and identifies HDRS17 Responders as a secondary outcome. It does not provide a numerical result for that outcome in the registry record recorded. The number of analyses listed is zero, and no inferential analysis details are reported. This does not demonstrate that no analysis was performed; it means that analysis entries and their methods are not reported in the registry record.
A planning illustration based on an observed effect answers a different question from the trial's observed result. The stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect set as a fraction of the observed effect. Such calculations describe hypothetical planning under those assumptions and should be read as participants per arm for a chosen power level, where those outputs are presented. They are not observed power, do not show the trial was adequately powered, and are not the trial's reported sample-size justification. The registry does not report that justification.
In general, over-dispersion matters when observed variability is greater than a model expects: standard errors can then be too small if the extra variability is ignored. That concern is relevant to some count-data models, but the primary outcome in this record is a remission proportion and no count-model analysis is reported. The record does not state that an over-dispersion model was used, so no such method should be inferred from the endpoint type or the planning assumptions.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the HDRS17 remission percentage as the primary outcome and HDRS17 Responders as a secondary outcome. It reports two outcome measures overall, but the numerical secondary result is not included in the recorded details. A multiplicity adjustment, outcome hierarchy, or strategy for interpreting more than one endpoint is not reported in the registry record. Without those details, it is not possible to determine how the investigators planned to account for multiple statistical comparisons.
The primary result is identified as ITT LOCF. In general, this label combines an intention-to-treat population with a last-observation-carried-forward approach to missing measurements. The registry does not give participant flow, the number of missing Week 6 assessments, reasons for missingness, or the number of participants included in each outcome analysis. It also does not report sensitivity analyses that could show whether conclusions change under other assumptions about missing outcomes.
Details about exclusions, protocol deviations, adherence, and the handling of participants with no post-baseline measurement are not reported in the registry record. Nor are interim analyses, stopping rules, or a prespecified statistical analysis plan reported. These omissions do not establish that such procedures were absent; they mean the registry record does not document them. Accordingly, the posted percentages should be read as the reported primary outcome values for the stated analysis population, without assuming a multiplicity procedure or a particular missing-data rule beyond the ITT LOCF label.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Adjunct Oral SAMe Tosylate 800mg PO BiD | 0 | 39 | 0.0% |
| Oral Adjunct Placebo | 0 | 34 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Adjunct Oral SAMe Tosylate 800mg PO BiD | 20 of 39 |
| Oral Adjunct Placebo | 19 of 34 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Adjunct Oral SAMe Tosylate 800mg PO BiD | Oral Adjunct Placebo |
|---|---|---|---|
| Upper gastrointestinal upset | Gastrointestinal disorders | 14 of 39 | 7 of 34 |
| Diarrhea | Gastrointestinal disorders | 7 of 39 | 5 of 34 |
| Activation | Nervous system disorders | 3 of 39 | 4 of 34 |
| Insomnia | Nervous system disorders | 4 of 39 | 2 of 34 |
| Somnolence and fatigue | Nervous system disorders | 4 of 39 | 2 of 34 |
| Headache | Nervous system disorders | 4 of 39 | 2 of 34 |
| Vivid dreams | Nervous system disorders | 0 of 39 | 2 of 34 |
The serious adverse event figures list zero affected participants in the SAMe arm, among 39 at risk, and zero in the placebo arm, among 34 at risk. The registry does not list serious adverse event terms. These entries describe the posted serious-event counts; they do not establish that no safety events of any kind occurred.
For other adverse events, the registry lists 20 affected participants among 39 at risk in the SAMe arm and 19 among 34 at risk in the placebo arm. These are the counts as recorded, not a comparison adjusted for follow-up time or other factors. The record does not define the event-counting rules, describe event severity beyond the serious/non-serious grouping, or give a breakdown by event type in the registry record recorded.
Deaths are not reported in the registry record. Safety counts need context, including how events were collected, their duration and seriousness, and whether participants could experience more than one event. Those details are not reported. The figures should therefore be read as registry summaries, not as a complete account of harms or as a basis for medical decisions.
12. What the Result Does, and Does Not, Mean
The posted result answers a specific descriptive question: what percentage of the registered ITT LOCF population met the HDRS17 remission definition at Week 6 in each arm? The registry reports 46.1% for adjunct SAMe and 17.6% for adjunct placebo. The endpoint definition is explicit, and the group sizes are reported as 39 and 34.
Those values do not by themselves establish the size or precision of a treatment effect. The record does not report a confidence interval, p-value, adjusted comparison, or exact number of remitters. It also does not provide the information needed to assess the assumptions behind the ITT LOCF result or the effects of missing outcome data. A numerical contrast between the percentages should not be substituted for a reported inferential analysis.
The registered study concerns SAMe added to antidepressant treatment among people described as not having responded to antidepressants alone. It does not establish that the findings apply to other populations, treatment settings, antidepressant regimens, assessment times, or outcome definitions. The registry does not provide detailed eligibility criteria or participant characteristics with which to judge generalizability.
In general, an observed difference between randomized groups can be informative, but uncertainty and design details are needed to interpret it responsibly. The listed design is randomized and double-masked, yet the record does not describe allocation procedures, masking details, or the statistical plan. The result is therefore best understood as the reported Week 6 remission proportions within this trial's stated analysis population, rather than as a complete estimate of benefit, harm, or clinical effectiveness.
Nothing in these data alone gives individualized guidance. The registry's percentages are a trial-level summary, and the missing inferential and clinical details constrain what can be concluded from them.
13. Why This Trial Matters Statistically
Statistically, the trial focuses on a binary endpoint derived from a symptom scale: participants either met the defined remission threshold at Week 6 or did not. This makes the outcome readily interpretable as a proportion, while also discarding distinctions among scores within each category. The endpoint's definition and time point are stated, allowing the reader to understand what the reported percentages represent.
The record also makes visible a common distinction between a point result and its precision. It reports the remission proportions and arm sizes, but no confidence interval or p-value for the comparison. In general, estimates need uncertainty measures to show how much the data constrain plausible values. Their absence limits statistical interpretation even when the endpoint and observed percentages are clear.
The ITT LOCF label raises an important missing-data issue. In general, carrying a prior observation forward can affect a final-outcome proportion because an imputed score may fall on either side of the remission threshold. Without missingness counts, timing, or sensitivity analyses, readers cannot tell how much the posted result depends on that approach. This is a reason to distinguish the reported result from a fully documented analysis.
The registry record also illustrates how limited analysis reporting affects reproducibility. The study is labeled randomized, double-masked, and parallel, but details of allocation, masking, and the statistical analysis are not reported. The primary result can be stated accurately, while important questions about inference, multiplicity, and missing data remain open. That separation between what is recorded and what remains undocumented is itself useful when evaluating a clinical trial statistically.
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.
Several trial-specific details needed to evaluate the remission result are not reported in the registry record. These include the participant eligibility criteria, baseline clinical characteristics, background antidepressant regimens, allocation procedures, and details of who was masked. Without those details, it is not possible to assess the enrolled population's characteristics or the operational conduct of the trial from this record alone.
The primary endpoint is reported as percentages, but exact remitter counts and score distributions are not given. No confidence interval, p-value, effect estimate, or model specification is reported. As a result, the precision of the arm-specific proportions and the statistical evidence for a between-arm contrast cannot be determined from the registry information.
The ITT LOCF analysis label is not accompanied by missingness counts, reasons for missing data, participant flow, or sensitivity analyses. The assumptions and exact implementation of carrying observations forward therefore cannot be assessed. The registry also does not report the planned sample-size justification, target power, interim monitoring, or analysis plan. Planning illustrations based on observed effects do not fill those gaps and are not evidence of observed power.
The record lists HDRS17 Responders as a secondary outcome but does not report its numerical result or a multiplicity strategy. Safety information is limited to the posted serious and other adverse-event counts; event terms, collection details, and deaths are not reported in the registry record. These limitations reflect what is documented in the record and should not be taken as proof that unreported procedures or information did not exist.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Optimizing the Effectiveness of Selective Serotonin Reuptake Inhibitors (SSRIs) in Treatment-Resistant Depression — NCT00093847.
- Registry record last updated 2014-10-13; status last verified 2014-10.
- Results first posted 2014-10-13.
- 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.
Continue through the Clinical Biostats statistical pathway
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18. Record Summary
NCT00093847 is a completed phase 2 randomized, double-masked, parallel trial sponsored by Massachusetts General Hospital. It enrolled 73 participants, with a recorded start date of 2004-05 and primary completion date of 2009-02. The study examined adjunct oral SAMe tosylate versus oral adjunct placebo for depression described as treatment-resistant.
The primary endpoint was the percentage meeting the HDRS17 remission definition, a final score of 7 or less, at Week 6. The registry reports 46.1% in the SAMe arm and 17.6% in the placebo arm, using an ITT LOCF population. The arm sizes were 39 and 34. Serious adverse events were listed as zero in both arms; other adverse events affected 20 and 19 participants, respectively. Deaths are not reported in the registry record.
No primary comparison estimate, confidence interval, p-value, analysis method, missing-data details, or numerical secondary result is reported. The registry lists HDRS17 Responders as a secondary outcome.