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 Methotrexate Compared With Dactinomycin in Treating Patients With Gestational Trophoblastic Neoplasia (NCT00003702), a randomized phase 3 study. The primary outcome is Response Based on Blood Human Chorionic Gonadotropin (hCG) Assay.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00003702 |
| Phase | Phase 3 |
| Condition | Good Prognosis Metastatic Gestational Trophoblastic Tumor, Hydatidiform Mole, Non-Metastatic Gestational Trophoblastic Tumor |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 240 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Gynecologic Oncology Group |
| Results posted | Yes |
2. Clinical Question
Population
Eligible patients who received a random treatment allocation for gestational trophoblastic neoplasia.
Intervention
Methotrexate given intramuscularly once weekly, with treatment continued until the hCG criterion was met and followed by consolidation treatment.
Comparator
Dactinomycin given intravenously every two weeks, with treatment continued until the same hCG criterion was met and followed by consolidation treatment.
Primary question
How did the proportion meeting the complete-response definition compare between the randomized treatment arms?
The registry frames this as a comparison of methotrexate with dactinomycin as primary management for low-risk gestational trophoblastic neoplasia. Its primary endpoint is response based on blood human chorionic gonadotropin (hCG) assay. Complete response is defined as a normal hCG sustained over four weekly measurements. The planned comparison is between proportions responding in the treatment arms, rather than a comparison of time until response.
The clinical question therefore concerns whether the response proportions differed under the two assigned treatment regimens. It does not ask whether the regimens have identical schedules: methotrexate is weekly and intramuscular, whereas dactinomycin is administered intravenously every two weeks. The registry also describes additional consolidation treatment after the hCG criterion is reached.
The primary outcome population is described as eligible patients who received a random treatment allocation. However, the registry record does not report the primary response counts, the estimated difference between arms, or a test result. It therefore does not establish the direction, size, or precision of the response comparison. The listed conditions include good-prognosis metastatic and non-metastatic gestational trophoblastic tumor, hydatidiform mole, and uterine corpus choriocarcinoma; the record does not give subgroup-specific primary results.
3. Trial Design
The registry describes a randomized, parallel-group phase III trial with no masking. It lists a planned enrollment of 240 and a completed status. The recorded start is 1999-06, and primary completion is recorded as 2010-07. The sponsor is the Gynecologic Oncology Group. The official title describes the comparison as weekly parenteral methotrexate versus “pulsed” dactinomycin as primary management for low-risk gestational trophoblastic neoplasia.
In the methotrexate arm, participants were to receive methotrexate intramuscularly once weekly in the absence of disease progression or unacceptable toxicity. Treatment continued until one beta hCG titer was below the institutional normal, followed by one additional consolidation treatment. In the dactinomycin arm, participants were to receive dactinomycin intravenously over 15 minutes every two weeks, subject to the same progression and toxicity conditions. Treatment continued until the same hCG criterion was met, followed by one additional consolidation treatment.
Random allocation supports a comparison of assigned strategies, but the registry does not report the sequence-generation method, allocation concealment, or other details of how randomization was implemented. No masking is recorded. The parallel-group structure means participants were assigned to a treatment arm rather than crossing between regimens, but further operational details are not reported in the registry record.
The planned enrollment is not an observed analysis population. Safety entries list 107 participants at risk in each arm, but those entries do not substitute for the missing primary-outcome denominators or explain exclusions and follow-up. The record does not report a protocol-based sample-size justification. It also does not report whether enrollment met the planned target or how many participants contributed to each primary-outcome analysis.
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
| Stage | Arm 1: Methotrexate 30 mg/m2 IM Weekly | Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks |
|---|---|---|
| STARTED | 120 | 120 |
| COMPLETED | 107 | 109 |
| NOT COMPLETED | 13 | 11 |
Reasons for not completing this period:
| Reason | Arm 1: Methotrexate 30 mg/m2 IM Weekly | Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks |
|---|---|---|
| Ineligible cell types | 2 | 2 |
| Did not meet criteria for persistence | 8 | 5 |
| WHO score > 6 | 2 | 1 |
| Inadequate documentation of disease | 1 | 3 |
Analysis population for the primary outcome, as defined in the registry: Eligible patients who received a random treatment allocation
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: Eligible participants
| Characteristic | Unit | Arm 1: Methotrexate 30 mg/m2 IM Weekly | Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks | Total |
|---|---|---|---|---|
| Participants analysed | 107 | 109 | 216 | |
| Age, Continuous | years | 28.8 (SD 7.9) | 30.4 (SD 8.6) | 29.6 (SD 8.3) |
| Sex: Female, Male: Female | Participants | 107 | 109 | 216 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Response Based on Blood Human Chorionic Gonadotropin (hCG) Assay, measured over Endpoint was assessed by hCG measurements taken weekly, once normal, treatment was bi-weekly, then monthly, up to 12 months..
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is response based on a blood hCG assay. The registry describes the primary comparison as the difference in the proportion responding between treatment arms, evaluated using a chi-square test. A complete response is defined as a normal hCG sustained over four weekly measurements. The outcome is therefore treated as a categorical response: participants either meet the stated complete-response criterion or do not, according to the endpoint definition.
The record describes serial measurement: hCG was assessed weekly, then treatment was given bi-weekly once levels were normal, and assessments continued monthly, up to 12 months. This schedule provides repeated observations relevant to determining whether the hCG response is sustained. The endpoint definition uses the sustained normal result rather than a single measurement, which makes the response criterion explicit in relation to the measurement schedule.
In general, a binary endpoint can make a treatment comparison easier to interpret as a difference in the proportions meeting a prespecified condition. That simplicity comes with a loss of detail: a binary response does not, by itself, describe how quickly response occurred, the pattern of measurements, or the range of hCG changes among participants who did not meet the criterion. Those are general properties of binary outcomes, not additional findings from this trial.
The registry record does not report the primary response counts or the result of the stated test. Thus the endpoint can be described, but the response proportions and their uncertainty cannot be assessed from the reported primary results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record sets out a randomized comparison of two treatment regimens and defines a complete response using serial hCG measurements. It also specifies that the primary comparison concerns the difference in response proportions and names a chi-square test. These details describe the intended outcome and comparison, but they are not a report of the trial’s primary analysis.
No primary response counts, response proportions, effect estimate, confidence interval, or test result are reported in the registry record. The primary outcome is not reduced to one comparison in the posted results, and the record lists no analyses. Consequently, the magnitude and direction of any difference cannot be established from the primary outcome information recorded. Its precision also cannot be evaluated: without an effect estimate and an uncertainty measure, there is no basis for judging how compatible the results are with a range of possible differences.
The adverse-event entries contain counts, but they answer a different question from the primary efficacy endpoint. For serious adverse events, the record lists zero affected participants among 107 at risk in the methotrexate arm and one among 107 at risk in the dactinomycin arm. For other adverse events, it lists 50 affected among 107 at risk in the methotrexate arm and 68 among 107 at risk in the dactinomycin arm. These entries should be read as reported safety counts, not as a substitute for the response comparison. The record does not give a statistical comparison or uncertainty for these safety counts.
The planned enrollment of 240 is a design-record figure, whereas the safety entries give their own at-risk counts. These figures refer to different aspects of the record and should not be combined to infer an analyzed primary sample size. The record does not state why the safety denominators differ from the planned enrollment, or whether all enrolled participants were eligible for each analysis.
Overall, the registry record supports a description of the randomized design, treatment schedules, endpoint definition, and reported adverse-event counts. It does not support a numerical conclusion about which arm had a higher complete-response proportion, whether the arms differed statistically, or how precisely such a difference was estimated. Those questions require primary outcome results and their analysis, which are not reported in the registry record.
9. Statistical Methods Explained
The planned primary analysis compares response proportions between treatment arms using a chi-square test. The registry defines complete response as normal hCG sustained over four weekly measurements and identifies eligible patients who received a random treatment allocation as the primary outcome population. The method and endpoint definition can be explained, but the primary result itself is not reported in the registry record.
What does a comparison of proportions test?
A proportion is the share of participants in an arm who meet a defined outcome. For this trial, that outcome is complete response under the registry’s hCG definition. A chi-square test evaluates whether the observed distribution across response categories is compatible with the hypothesis of no association between treatment arm and response category. The test does not, by itself, describe the size or clinical importance of a difference. For that, readers need the response proportions and an effect estimate, ideally accompanied by an interval expressing uncertainty.
The test’s interpretation depends on the outcome counts and the analysis population. The registry record does not report the number meeting the complete-response definition in either arm, the number included in the primary analysis, or a chi-square statistic or p-value. Therefore, it is not possible to reproduce or interpret the stated primary test from the record. A test name in an outcome description is not evidence that its result has been posted.
What would a confidence interval contribute?
In general, a confidence interval expresses the uncertainty around an estimated effect under the assumptions of the analysis. For a difference in response proportions, it would indicate which values of the difference are compatible with the observed data and method. A narrow interval indicates greater precision than a wide interval, while an interval spanning values on both sides of no difference may leave the direction uncertain. These are general statistical explanations; no primary effect estimate or confidence interval is reported for this trial in the registry record.
A p-value and a confidence interval answer related but distinct questions. A p-value summarizes how unusual the data would be under a specified null model, while an interval conveys a range of effect values compatible with the data under its method. Neither alone establishes whether an observed difference is important. Because neither a primary p-value nor a primary interval is reported, the registry record does not permit those interpretations for the response endpoint.
What is the role of the treatment schedule?
The endpoint uses repeated hCG measurements, and the treatment schedules differ in administration route and frequency. The primary analysis is described as a comparison of response proportions, not as an analysis of time to response. A binary response comparison can capture whether the stated criterion was met, but it does not retain all information about when response occurred or how measurements changed over time. A time-to-event analysis would address a different question and would require its own outcome definition and analysis details; these are not reported as the primary analysis.
More generally, longitudinal measurements can be analyzed in several ways, and the choice should match the scientific question and the structure of the observations. The registry describes the measurement schedule but does not report a model for repeated hCG values. It would therefore be inappropriate to infer that a particular longitudinal model, adjustment, or time-to-event method was used.
How should planning illustrations be understood?
The record describes sample-size illustrations using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The illustrations are based on a stated fraction of an observed effect, and they are explicitly not the trial’s own design calculation. Such illustrations are planning exercises: they show what sample sizes would correspond to their assumptions. They are not observed power, do not establish the trial’s original sample-size justification, and do not replace a reported treatment-effect estimate with its uncertainty.
The registry record does not report the trial’s own sample-size justification or a primary effect estimate. Without those results, the assumptions underlying an illustration cannot be checked against the trial’s observed response data. Its values should not be interpreted as evidence that the study had a particular probability of detecting an effect, nor as an outcome analysis.
What does over-dispersion mean in general?
For count outcomes, over-dispersion occurs when variability is greater than a statistical model expects. If a model assumes less variation than the data contain, uncertainty estimates can be too small and inferential results can appear more certain than warranted. This is a general concept, not a reported feature of this trial. The primary endpoint is described as a response proportion, and the registry record does not report an over-dispersion assessment or a count model. No claim about over-dispersion in these trial data can be made from the posted record.
More broadly, statistical interpretation depends on the match between the endpoint, estimand, population, and analysis. The registry names a response-based question and a chi-square test, but does not report the primary counts or analysis output. The design information is useful for understanding what comparison was intended; it cannot fill the gap left by the unreported primary result.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three outcome measures, names a secondary outcome concerning the number of patients with a decline of hCG on day 1 of treatment, and reports no analyses. The primary outcome description identifies a comparison of response proportions, but the primary result is not reported. The other outcome measures are not characterized in enough detail in the registry record to explain their role in the analysis.
When a trial evaluates multiple outcomes, time points, subgroups, or alternative analyses, the chance of a nominally unusual result can increase if many tests are considered without accounting for that multiplicity. A statistical plan may specify which outcome is primary and how other tests will be interpreted. The registry record does not report a multiplicity adjustment or a detailed plan for handling multiple comparisons. It is therefore not possible to determine whether or how multiplicity was addressed in the trial analysis.
The outcome description includes a measurement schedule extending up to 12 months, but the record does not provide a full account of all time-point analyses. The presence of repeated measurements does not by itself show that multiple tests were performed; their analysis and any multiplicity approach are not reported in the registry record.
Missing-data handling is also not reported in the registry record. There is no description of how participants with incomplete hCG measurements, withdrawal, or other unavailable outcome data were treated. The primary outcome population is described as eligible patients who received a random treatment allocation, but the record does not state whether the analysis followed that population as assigned, how deviations were handled, or how many participants contributed to the primary endpoint. The description is not enough to label the analysis as intention-to-treat or to assess the effect of missing observations.
These omissions limit reproducibility and interpretation. They do not establish that missing data or multiplicity caused bias; they mean the registry record does not provide the information needed to evaluate those possibilities.
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 |
|---|---|---|---|
| Arm 1: Methotrexate 30 mg/m2 IM Weekly | 0 | 107 | 0.0% |
| Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks | 1 | 107 | 0.9% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm 1: Methotrexate 30 mg/m2 IM Weekly | 50 of 107 |
| Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks | 68 of 107 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm 1: Methotrexate 30 mg/m2 IM Weekly | Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks |
|---|---|---|---|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 0 of 107 | 1 of 107 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm 1: Methotrexate 30 mg/m2 IM Weekly | Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 8 of 107 | 21 of 107 |
| Constitutional | General disorders | 12 of 107 | 15 of 107 |
| Pain | General disorders | 13 of 107 | 14 of 107 |
| Neutropenia | Blood and lymphatic system disorders | 6 of 107 | 20 of 107 |
| Hemorrhage | Blood and lymphatic system disorders | 9 of 107 | 13 of 107 |
| Anemia | Blood and lymphatic system disorders | 7 of 107 | 14 of 107 |
| Gastrointestinal | Gastrointestinal disorders | 7 of 107 | 14 of 107 |
| Vomiting | Gastrointestinal disorders | 3 of 107 | 14 of 107 |
| Infection/Fever | Infections and infestations | 7 of 107 | 4 of 107 |
| Neurologic | Nervous system disorders | 6 of 107 | 5 of 107 |
Serious events with the highest arm-level rate: dyspnea (0.9%).
The safety entries distinguish serious adverse events from other adverse events and give the number at risk and the number affected in each arm. The methotrexate arm lists zero serious adverse events among 107 at risk and 50 other adverse events among 107 at risk. The dactinomycin arm lists one serious adverse event among 107 at risk and 68 other adverse events among 107 at risk. These are counts as recorded, not a statistical comparison.
The registry also lists dyspnea at 0.9% among the top serious adverse-event terms. It does not attribute that term to a particular arm in the recorded summary. The serious-event count and the term listing should therefore be read with care rather than treated as a complete description of all event types or their distribution.
Counts of participants affected do not show event severity beyond the serious-versus-other classification, duration, recurrence, or the number of events per participant. The registry record does not report a comparative safety analysis, uncertainty estimates, or a detailed account of ascertainment and follow-up for adverse events. These figures describe the posted safety entries only and should not be read as establishing a difference between regimens.
12. What the Result Does, and Does Not, Mean
The record documents a randomized phase III trial designed to compare methotrexate and dactinomycin for low-risk gestational trophoblastic neoplasia. It specifies treatment schedules, a complete-response definition based on sustained normal hCG, and a planned comparison of response proportions using a chi-square test. These features identify the clinical question the trial set out to address.
The primary outcome result is not reported in the registry record. Without response counts, an effect estimate, an interval, or a test result, the posted record cannot show whether the arms had similar or different response proportions, which arm had a larger proportion, or how precise an estimated difference would be. It also cannot support a conclusion that either regimen is superior or equivalent on the primary endpoint.
The safety entries provide descriptive counts, including the serious-event counts and other adverse-event counts by arm. They do not include a formal comparison or uncertainty measure. They should not be taken as a complete characterization of safety, nor do they answer the primary response question.
In general, the absence of a reported result is not the same as a finding of no difference. A conclusion of no meaningful difference would require suitable results and a prespecified interpretation framework; neither is reported in the registry record. Similarly, a completed status does not by itself provide the outcome estimates needed to interpret trial findings.
The record supports conclusions about what was planned and how the outcomes were defined, as well as a limited description of recorded safety counts. It does not support a treatment recommendation or a clinical judgment about effectiveness. Those would require complete results and interpretation in context, which are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial illustrates why a registry entry can be informative about design without being sufficient for an effect estimate. Random allocation, the parallel-group structure, treatment schedules, and the hCG-based response definition establish the intended comparison. The record also states the proposed statistical test. These elements make the scientific question understandable and identify the analysis that the registry says was planned.
At the same time, a named endpoint and test do not reveal the observed treatment effect. The primary response counts and analysis results are not reported, so readers cannot assess magnitude, direction, precision, or statistical compatibility with a null difference. This distinction is central to statistical literacy: plans describe what investigators intended to measure, while results show what the data estimated.
The endpoint also demonstrates the trade-off involved in categorizing a continuous biomarker and its repeated measurements into a response status. A clear threshold-based definition can support a direct comparison of proportions, but it does not describe the full pattern of hCG measurements or timing of response. This is a general statistical observation about binary endpoints, not a claim about the trial’s unreported findings.
The safety entries offer another useful distinction. Counts can be reported without a comparative estimate or uncertainty assessment. They should be interpreted descriptively and separately from the primary response analysis. The record’s incomplete analysis details also show why denominators, missing-data handling, multiplicity plans, and analysis populations matter when readers evaluate evidence.
Finally, planning illustrations are not the same as the trial’s own design rationale or observed power. Separating planning assumptions from observed results prevents a calculation from being mistaken for evidence about the outcome. Together, these points make the record a useful example of how design information, outcome definitions, and actual statistical findings serve different roles.
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 most important trial-specific limitation for interpreting the registry entry is that the primary response results are absent. The record defines complete response and names a chi-square comparison, but does not report response counts, proportions, an effect estimate, an uncertainty interval, or a test result. The primary endpoint therefore cannot be quantitatively interpreted from the record.
The available safety denominators are recorded as 107 at risk in each arm, while planned enrollment is 240. The registry record does not explain the relationship between these figures or identify the primary analysis denominators. No primary analysis population count is reported, so the safety entries should not be used to infer how many participants contributed to the response analysis.
The record describes weekly hCG measurement, followed by bi-weekly treatment once hCG was normal and monthly measurements up to 12 months. It does not provide a full account of outcome ascertainment at each time point, missing measurements, or handling of participants who discontinued or were otherwise not evaluable. The reason for missing primary results is also not reported in the registry record.
Further details that would help evaluate the trial are not reported in the registry record, including randomization implementation, the sample-size justification, a detailed statistical analysis plan, multiplicity procedures, and methods for missing data. No masking is recorded, but the record does not explain whether outcome assessment was blinded. These absences limit assessment of the robustness and reproducibility of any primary analysis.
These are limitations of the available registry information. They should not be mistaken for proof that the trial itself lacked procedures or that its results were biased; those matters are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Methotrexate Compared With Dactinomycin in Treating Patients With Gestational Trophoblastic Neoplasia — NCT00003702.
- Registry record last updated 2018-05-15; status last verified 2016-02.
- Results first posted 2018-05-15.
- 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
NCT00003702 is a completed randomized phase III parallel-group trial sponsored by the Gynecologic Oncology Group. The registry lists planned enrollment of 240, no masking, a recorded start of 1999-06, and primary completion in 2010-07. It compares weekly intramuscular methotrexate with intravenous dactinomycin given every two weeks.
The primary outcome is response based on blood hCG assay, with complete response defined as normal hCG sustained over four weekly measurements. The stated comparison is a difference in response proportions evaluated using a chi-square test. The primary response results and analyses are not reported in the registry record.
Safety entries list zero serious adverse events among 107 at risk in the methotrexate arm and one among 107 at risk in the dactinomycin arm. Other adverse-event counts are 50 and 68, respectively, among 107 at risk in each arm. These are descriptive entries; the record does not report a comparative safety analysis.