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 Safety and Tolerability of IC83/LY2603618 Administered After Pemetrexed 500 mg/m2 Every 21 Days in Patients With Cancer (NCT00415636), a non-randomized phase 1 study. The primary outcome is Number of Participants With Adverse Events (AEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00415636 |
| Phase | Phase 1 |
| Condition | Cancer |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 31 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eli Lilly and Company |
| Results posted | Yes |
2. Clinical Question
Population
Patients with cancer. The registry reports enrollment of 31 participants and defines the safety population as participants who received any amount of LY2603618. The numbers in the safety summaries are reported separately for the LY2603618 dose groups.
Intervention
LY2603618 was administered after pemetrexed, as described in the study title. The registry lists LY2603618 dose groups at 40 mg/m^2, 70 mg/m^2, 105 mg/m^2, 150 mg/m^2, and 195 mg/m^2. The 40 mg/m^2 dose was administered using either a 4.5-hour infusion or a 1-hour infusion.
Comparator
There was no randomized control group. The record describes a non-randomized, single-group study with different dose cohorts; those cohorts are not like-for-like control groups. Comparisons between them cannot isolate dose effects from other differences between cohorts.
Primary question
The primary outcome was the number of participants with adverse events, from baseline up to 24 months. The safety summaries distinguish serious adverse events from all other non-serious adverse events. This is a safety and tolerability question, not a randomized test of treatment benefit.
The study’s stated purpose was to evaluate the safety and tolerability of IC83/LY2603618 for cancer treatment. Its phase 1 dose-escalation structure focused on administering LY2603618 at different dose levels after pemetrexed. The registry title specifies pemetrexed 500 mg/m^2 every 21 days, while the arm descriptions give additional details about LY2603618 dose and infusion duration.
The primary outcome concerns whether participants experienced adverse events, with the observation timeframe stated as baseline up to 24 months. The registry also names pharmacokinetic outcomes and best overall response as secondary outcomes. The registry record does not report a randomized comparison or a control-arm estimate. It therefore supports a descriptive reading of safety observations in the listed cohorts, rather than a causal comparison of LY2603618 with an alternative treatment.
3. Trial Design
The registry describes a phase 1, non-randomized, unmasked, single-group study. The study is titled as a dose-escalation investigation of LY2603618 administered after pemetrexed in patients with cancer. Enrollment was 31. The record lists the study as completed, with a start date of 2007-01 and primary completion in 2010-03. Eli Lilly and Company is named as the sponsor.
The LY2603618 groups reflect a sequence of dose and infusion regimens. At 40 mg/m^2, one cohort received a 4.5-hour infusion, consisting of a 30-minute bolus followed by a 4-hour infusion; dose modifications were not allowed. Another cohort received the same dose over 1 hour, also without dose modifications. The description says the 1-hour regimen followed pharmacokinetic data from the 4.5-hour cohort. The 70 mg/m^2 cohort received LY2603618 over 1 hour, and dose modifications were allowed beginning with that cohort. The 105 mg/m^2, 150 mg/m^2, and 195 mg/m^2 cohorts also received LY2603618 over 1 hour.
The registry does not describe randomized allocation or masking, and the arm structure does not supply a concurrent control group. Consequently, differences in outcomes between cohorts are descriptive. Dose level, infusion schedule, cohort membership, and the allowance of dose modifications are not independently randomized factors. The registry record does not report additional details about the dose-escalation decision rules, the protocol’s sample-size justification, interim analyses, or a statistical analysis plan.
The primary endpoint was the number of participants with adverse events, with the timeframe stated as baseline up to 24 months. The safety population included all participants who received any amount of LY2603618. The registry directs readers to its adverse event module for summaries of serious adverse events and all other non-serious adverse events.
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 | LY2603618 40 mg/m^2 (4.5-hour Infusion) | LY2603618 40 mg/m^2 (1-hour Infusion) | LY2603618 70 mg/m^2 | LY2603618 105 mg/m^2 | LY2603618 150 mg/m^2 | LY2603618 195 mg/m^2 |
|---|---|---|---|---|---|---|
| STARTED | 3 | 3 | 3 | 13 | 6 | 3 |
| COMPLETED | 2 | 3 | 2 | 7 | 4 | 1 |
| NOT COMPLETED | 1 | 0 | 1 | 6 | 2 | 2 |
Reasons for not completing this period:
| Reason | LY2603618 40 mg/m^2 (4.5-hour Infusion) | LY2603618 40 mg/m^2 (1-hour Infusion) | LY2603618 70 mg/m^2 | LY2603618 105 mg/m^2 | LY2603618 150 mg/m^2 | LY2603618 195 mg/m^2 |
|---|---|---|---|---|---|---|
| Symptomatic deterioration | 1 | 0 | 1 | 2 | 0 | 1 |
| Adverse Event | 0 | 0 | 0 | 1 | 1 | 0 |
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 |
| Disease progression | 0 | 0 | 0 | 3 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The safety population was comprised of all participants who received any amount of LY2603618.
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.
Only the first 6 of 7 groups are shown.
| Characteristic | Unit | LY2603618 40 mg/m^2 (4.5-hour Infusion) | LY2603618 40 mg/m^2 (1-hour Infusion) | LY2603618 70 mg/m^2 | LY2603618 105 mg/m^2 | LY2603618 150 mg/m^2 | LY2603618 195 mg/m^2 |
|---|---|---|---|---|---|---|---|
| Participants analysed | 3 | 3 | 3 | 13 | 6 | 3 | |
| Age, Continuous | years | 49.0 (SD 6.24) | 58.0 (SD 10.54) | 48.3 (SD 16.07) | 60.6 (SD 9.95) | 63.5 (SD 11.04) | 55.7 (SD 18.77) |
| Sex: Female, Male: Female | Participants | 3 | 1 | 2 | 5 | 3 | 1 |
| Sex: Female, Male: Male | Participants | 0 | 2 | 1 | 8 | 3 | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 1 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | 3 | 3 | 12 | 6 | 3 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 1 |
| Race (NIH/OMB): Asian | Participants | 1 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 1 | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 2 | 3 | 2 | 13 | 6 | 2 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment: United States | Participants | 3 | 3 | 3 | 13 | 6 | 3 |
| Primary Cancer Type: Breast | Participants | 3 | 1 | 1 | 0 | 1 | 0 |
| Primary Cancer Type: Non-small Cell Lung | Participants | 0 | 0 | 0 | 1 | 0 | 0 |
| Primary Cancer Type: Pancreatic | Participants | 0 | 0 | 0 | 3 | 2 | 1 |
| Primary Cancer Type: Other | Participants | 0 | 2 | 2 | 9 | 3 | 2 |
| Eastern Cooperative Oncology Group (ECOG) Rating at Screening: ECOG Rating 0 | Participants | 2 | 1 | 0 | 4 | 1 | 0 |
| Eastern Cooperative Oncology Group (ECOG) Rating at Screening: ECOG Rating 1 | Participants | 1 | 2 | 3 | 9 | 5 | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events (AEs), measured over baseline up to 24 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with adverse events. Its stated timeframe is baseline up to 24 months, and the defined safety population comprises participants who received any amount of LY2603618. The registry’s adverse-event summaries separate serious adverse events from all other non-serious adverse events.
A participant count is a direct way to describe how many people in a defined group experienced an event. It is different from a count of every event episode: a participant may have more than one event, while a participant-level outcome counts that person rather than each episode. The registry names a participant count as the primary outcome; further operational rules for determining which events qualify in that count are not reported in the registry record.
General statistical context: Safety outcomes are commonly central to early-phase studies because they describe adverse experiences during exposure and can inform subsequent investigation. A count alone does not describe event timing, duration, severity beyond the serious/non-serious grouping, or whether an event was attributed to study treatment. Those details require additional reporting. The record identifies the outcome and observation timeframe, and points to the adverse event module for detailed summaries, but the posted figures do not establish a causal relationship between LY2603618 and any event.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The safety summaries report both the number of participants at risk and the number affected by serious and other non-serious adverse events in each LY2603618 group. For serious adverse events, the groups are reported as 1 of 3 at 40 mg/m^2 with a 4.5-hour infusion; 0 of 3 at 40 mg/m^2 with a 1-hour infusion; 2 of 3 at 70 mg/m^2; 8 of 13 at 105 mg/m^2; 4 of 6 at 150 mg/m^2; and 2 of 3 at 195 mg/m^2. These are participant counts within dose groups, not counts of all individual serious-event episodes.
For all other non-serious adverse events, the registry reports 3 of 3 participants in each of the 40 mg/m^2 infusion groups, 3 of 3 at 70 mg/m^2, 13 of 13 at 105 mg/m^2, 6 of 6 at 150 mg/m^2, and 3 of 3 at 195 mg/m^2. These summaries are descriptive. They do not indicate how many distinct events each participant experienced, how long events lasted, or whether events were judged related to treatment.
The group sizes are small, and the cohorts were not randomized. A difference in the observed counts between dose groups cannot by itself establish that dose caused a difference in risk. The study also varied infusion duration at the 40 mg/m^2 dose, and the registry says dose modifications were allowed beginning with the 70 mg/m^2 cohort. Those design features further limit straightforward comparisons across groups. The record states that pharmacokinetic data informed the change in infusion duration, but it does not report a randomized comparison of infusion schedules.
The registry lists pancytopenia as a top serious adverse event term with 66.7%. It lists anaemia, cardiac arrest, abdominal pain, lower gastrointestinal haemorrhage, and pyrexia at 33.3% each. The record does not state the denominator used for these listed percentages in the material describing the terms, so they should not be read as percentages of a particular dose group. The percentages also do not, on their own, describe event severity, timing, attribution, or the number of episodes.
The primary endpoint is named as the number of participants with adverse events, but a single aggregate result for that endpoint is not reported in the registry record. The adverse-event module provides group-specific serious and other non-serious participant counts. Death counts are not reported in the registry record. No confidence intervals, hypothesis tests, or adjusted comparisons are reported; the number of analyses listed is 0. Thus the posted safety summaries describe what was recorded in the cohorts, but do not quantify uncertainty around comparative effects or support a causal treatment comparison.
9. Statistical Methods Explained
What does a participant count represent?
The primary outcome is a count of participants with adverse events, rather than a continuous measurement such as a laboratory value. For a participant-level safety outcome, the numerator is the number of people meeting the event definition and the denominator is the number of people in the relevant safety group. The registry’s adverse-event summaries give group sizes and affected-participant counts for serious and other non-serious events. Those counts should not be confused with the total number of event episodes: a participant can experience multiple events, and event-level totals may therefore differ from participant counts.
The outcome timeframe is baseline up to 24 months. A timeframe gives the window in which events are considered for the outcome; it does not reveal when events occurred within that window or how long they continued. The registry record does not report further details of event adjudication, such as the precise rules used to classify events or their relationship to treatment.
Why does the study structure matter?
Randomization is a general method for making comparison groups more similar, on average, with respect to measured and unmeasured factors. This study is explicitly non-randomized and is described as single-group, with sequential dose cohorts rather than a randomized control group. The listed cohorts therefore provide descriptive observations, not a randomized contrast. Differences in participant counts across dose groups may reflect factors other than dose, and the registry does not report an analysis that adjusts for such differences.
The regimen also changed across cohorts. The first two groups received the same LY2603618 dose using different infusion durations. Later cohorts received higher listed doses; dose modifications were allowed beginning with the 70 mg/m^2 group, whereas they were not allowed in the two 40 mg/m^2 groups. This structure makes it difficult to attribute any difference in observed safety counts to one treatment feature alone. The registry identifies a pharmacokinetic rationale for repeating the 40 mg/m^2 dose with a 1-hour infusion, but does not provide a randomized comparison of infusion duration.
How should uncertainty be considered?
General statistical context: A confidence interval expresses the range of values compatible with a dataset and an analysis method, under the assumptions used to construct it. For a small cohort, an estimate of an event proportion can be uncertain even when its observed count is clear. Confidence intervals for the posted safety comparisons are not reported in the registry record, so the precision of comparative estimates cannot be assessed from an interval estimate.
A hypothesis test or model-based comparison would require a defined analysis and assumptions appropriate to the design. The registry record does not report such an analysis for the primary safety outcome, and it lists 0 analyses. That absence means readers should not infer a statistical test from the descriptive counts. It also means there is no reported adjustment for possible differences between cohorts.
What role do planning calculations have?
General statistical context: Sample-size calculations can illustrate how many participants might be needed under specified assumptions, but they are not observed trial results. The registry’s planning illustrations are described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. The registry also distinguishes participant-per-arm illustrations from total-event illustrations for time-to-event outcomes. These assumptions do not establish that the study used that design: this trial is non-randomized and has no reported control arm. The registry record does not report the study’s own sample-size justification. Any planning illustration is not observed power and should not be interpreted as evidence that the study had a particular probability of detecting an effect.
More broadly, an observed result does not determine power after the fact. Power is a design quantity defined for a particular effect and analysis under specified assumptions. Planning calculations can help explore design scenarios, but they do not increase the information contained in the participants actually observed. The posted safety counts remain descriptive, and no comparative estimate or uncertainty interval is reported for them.
What can be concluded from the reported analyses?
The registry identifies a safety population and gives adverse-event counts by LY2603618 regimen. It names pharmacokinetic outcomes and best overall response as secondary outcomes, but the specific numerical results for those outcomes are not reported in the registry record in the information. The number of listed analyses is 0. Accordingly, the available statistical interpretation is limited to the safety counts and named outcomes; no inferential conclusion, adjustment, or estimate of comparative treatment effect is reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry names the number of participants with adverse events as the primary outcome. It also lists secondary outcomes for maximum observed plasma concentration, area under the plasma concentration-versus-time curve from time zero to infinity, and the percentage of participants with best overall response. These outcomes involve different kinds of measurements. The registry record does not report a multiplicity strategy describing how interpretation would account for examining several outcomes or analyses.
General statistical context: When several hypotheses are tested, the chance of at least one apparently unusual result can increase if each is treated as a separate test without adjustment. Multiplicity procedures can address this issue, but the choice depends on the analysis plan and the intended questions. No such procedure is reported in the registry record. The registry lists 0 analyses, so there are no reported hypothesis-test results to interpret or compare across outcomes.
Missing-data methods and the amount or pattern of missing outcome data are not reported in the registry record. The primary safety population is defined as participants who received any amount of LY2603618, but the record does not report a detailed analysis-population flow or explain how participants with incomplete follow-up were handled. The stated outcome timeframe is baseline up to 24 months; the registry does not report participant-level follow-up duration or the completeness of observation over that period.
The record names pharmacokinetic and response outcomes, but other analysis populations for those outcomes are not reported in the registry record. The safety summaries should therefore be read according to their stated safety population and group denominators, without assuming that every enrolled participant contributed to every outcome. A sample-size justification, interim-analysis plan, and statistical analysis plan are also not reported in the registry record.
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 |
|---|---|---|---|
| LY2603618 40 mg/m^2 (4.5-hour Infusion) | 1 | 3 | 33.3% |
| LY2603618 40 mg/m^2 (1-hour Infusion) | 0 | 3 | 0.0% |
| LY2603618 70 mg/m^2 | 2 | 3 | 66.7% |
| LY2603618 105 mg/m^2 | 8 | 13 | 61.5% |
| LY2603618 150 mg/m^2 | 4 | 6 | 66.7% |
| LY2603618 195 mg/m^2 | 2 | 3 | 66.7% |
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 |
|---|---|
| LY2603618 40 mg/m^2 (4.5-hour Infusion) | 3 of 3 |
| LY2603618 40 mg/m^2 (1-hour Infusion) | 3 of 3 |
| LY2603618 70 mg/m^2 | 3 of 3 |
| LY2603618 105 mg/m^2 | 13 of 13 |
| LY2603618 150 mg/m^2 | 6 of 6 |
| LY2603618 195 mg/m^2 | 3 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | LY2603618 40 mg/m^2 (4.5-hour Infusion) | LY2603618 40 mg/m^2 (1-hour Infusion) | LY2603618 70 mg/m^2 | LY2603618 105 mg/m^2 | LY2603618 150 mg/m^2 | LY2603618 195 mg/m^2 |
|---|---|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 0 of 3 | 0 of 3 | 0 of 3 | 1 of 13 | 1 of 6 | 1 of 3 |
| Pancytopenia | Blood and lymphatic system disorders | 0 of 3 | 0 of 3 | 0 of 3 | 0 of 13 | 0 of 6 | 2 of 3 |
| Small intestinal obstruction | Gastrointestinal disorders | 0 of 3 | 0 of 3 | 0 of 3 | 1 of 13 | 1 of 6 | 0 of 3 |
| Pyrexia | General disorders | 0 of 3 | 0 of 3 | 0 of 3 | 1 of 13 | 0 of 6 | 1 of 3 |
| Leukopenia | Blood and lymphatic system disorders | 0 of 3 | 0 of 3 | 0 of 3 | 1 of 13 | 0 of 6 | 0 of 3 |
| Neutropenia | Blood and lymphatic system disorders | 0 of 3 | 0 of 3 | 0 of 3 | 1 of 13 | 0 of 6 | 0 of 3 |
| Atrial fibrillation | Cardiac disorders | 0 of 3 | 0 of 3 | 0 of 3 | 1 of 13 | 0 of 6 | 0 of 3 |
| Cardiac arrest | Cardiac disorders | 0 of 3 | 0 of 3 | 1 of 3 | 0 of 13 | 0 of 6 | 0 of 3 |
| Abdominal pain | Gastrointestinal disorders | 0 of 3 | 0 of 3 | 1 of 3 | 0 of 13 | 0 of 6 | 0 of 3 |
| Diarrhoea | Gastrointestinal disorders | 0 of 3 | 0 of 3 | 0 of 3 | 1 of 13 | 0 of 6 | 0 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | LY2603618 40 mg/m^2 (4.5-hour Infusion) | LY2603618 40 mg/m^2 (1-hour Infusion) | LY2603618 70 mg/m^2 | LY2603618 105 mg/m^2 | LY2603618 150 mg/m^2 | LY2603618 195 mg/m^2 |
|---|---|---|---|---|---|---|---|
| Fatigue | General disorders | 0 of 3 | 3 of 3 | 3 of 3 | 4 of 13 | 5 of 6 | 2 of 3 |
| Nausea | Gastrointestinal disorders | 2 of 3 | 2 of 3 | 3 of 3 | 7 of 13 | 2 of 6 | 0 of 3 |
| Vomiting | Gastrointestinal disorders | 1 of 3 | 0 of 3 | 3 of 3 | 5 of 13 | 3 of 6 | 0 of 3 |
| Neutropenia | Blood and lymphatic system disorders | 0 of 3 | 1 of 3 | 1 of 3 | 5 of 13 | 3 of 6 | 1 of 3 |
| Diarrhoea | Gastrointestinal disorders | 1 of 3 | 1 of 3 | 1 of 3 | 5 of 13 | 3 of 6 | 0 of 3 |
| Constipation | Gastrointestinal disorders | 1 of 3 | 2 of 3 | 1 of 3 | 2 of 13 | 2 of 6 | 0 of 3 |
| Anaemia | Blood and lymphatic system disorders | 0 of 3 | 1 of 3 | 1 of 3 | 1 of 13 | 3 of 6 | 1 of 3 |
| Oedema peripheral | General disorders | 0 of 3 | 0 of 3 | 0 of 3 | 4 of 13 | 3 of 6 | 0 of 3 |
| Pyrexia | General disorders | 0 of 3 | 1 of 3 | 0 of 3 | 4 of 13 | 2 of 6 | 0 of 3 |
| Dehydration | Metabolism and nutrition disorders | 0 of 3 | 0 of 3 | 1 of 3 | 4 of 13 | 1 of 6 | 1 of 3 |
Serious events with the highest arm-level rate: pancytopenia (66.7%), anaemia (33.3%), cardiac arrest (33.3%), abdominal pain (33.3%), lower gastrointestinal haemorrhage (33.3%).
The serious adverse-event figures are participant counts by LY2603618 group. The registry reports 1 of 3 participants at 40 mg/m^2 with a 4.5-hour infusion, 0 of 3 at 40 mg/m^2 with a 1-hour infusion, 2 of 3 at 70 mg/m^2, 8 of 13 at 105 mg/m^2, 4 of 6 at 150 mg/m^2, and 2 of 3 at 195 mg/m^2. The corresponding group sizes are the participants reported at risk for those summaries.
These figures indicate how many participants were recorded as having a serious adverse event in each group; they are not the total number of serious-event episodes. The registry separately reports that all participants in each group had an adverse event classified as other than serious: 3 of 3 in each 40 mg/m^2 group, 3 of 3 at 70 mg/m^2, 13 of 13 at 105 mg/m^2, 6 of 6 at 150 mg/m^2, and 3 of 3 at 195 mg/m^2. These categories should not be added together to infer a number of unique participants, because the same participant may be represented in both categories.
The listed serious-event terms and percentages do not identify their dose-group distribution or provide an explicit percentage denominator in the registry record. Death counts are not reported in the registry record. The counts describe the posted safety observations; without a randomized control group or a reported comparative analysis, they do not establish that LY2603618 caused an event or that one dose regimen differed causally from another.
12. What the Result Does, and Does Not, Mean
The record documents a phase 1 study intended to examine the safety and tolerability of LY2603618 after pemetrexed in patients with cancer. It reports the numbers of participants with serious and other non-serious adverse events in the listed dose groups. The figures show that adverse events were recorded in each group, and that the serious-event participant counts varied across groups. They do not by themselves show why those counts differed.
The study was non-randomized, unmasked, and described as single-group. Its dose cohorts are not a like-for-like control comparison. Participants were not assigned at random to a LY2603618 dose, and the infusion schedule and allowance of dose modifications differed across the listed regimens. The cohort counts therefore cannot establish that a particular dose or infusion schedule caused a specific safety outcome.
The registry’s primary outcome is a participant count for adverse events over baseline up to 24 months. The record provides cohort-level safety counts, but an aggregate result for the primary outcome, confidence intervals, and formal comparative analyses are not reported in the registry record. The listed secondary outcomes concern pharmacokinetics and best overall response, but their numerical results are not reported in the registry record in the information. The safety findings do not establish treatment benefit, and they do not establish the absence of events beyond those summarized.
General statistical context: A descriptive count can be informative about what was observed in a study, but interpretation depends on the population, event definition, follow-up, and design. Small groups can yield imprecise estimates, and a difference between groups is not necessarily a treatment effect. The posted data should therefore be understood as safety observations from the enrolled cohorts, not as proof of a causal effect or as a comparison against an alternative treatment.
13. Why This Trial Matters Statistically
Statistically, this trial illustrates why design features must be considered alongside adverse-event counts. The registry reports safety observations across LY2603618 dose cohorts, but there is no randomized control group. Without random allocation, group differences can reflect participant characteristics, cohort-specific conditions, changes in regimen, or chance as well as any treatment-related effect. A numerical contrast between cohorts should not be treated as a causal estimate.
The study also shows why a participant-level count needs careful interpretation. The primary endpoint focuses on the number of participants with adverse events, while the adverse-event module distinguishes serious events from other non-serious events. Participant counts answer how many people were affected; they do not describe every event episode, its timing, duration, severity within a category, or attribution. Those dimensions require additional details.
The range of LY2603618 regimens is relevant to interpretation. The 40 mg/m^2 dose was administered with two infusion durations, while later cohorts used higher doses, and dose modifications were allowed beginning with the 70 mg/m^2 cohort. These features mean that a simple ordering of dose groups is not equivalent to a controlled dose-response experiment. The record’s note that pharmacokinetic data informed the infusion-duration change also emphasizes that regimen decisions were part of the study’s evolving structure.
Finally, the record names outcomes but reports no listed analyses, confidence intervals, or multiplicity approach. This distinction matters: outcome definitions and counts are not the same as inferential evidence. The study’s statistical value lies in documenting safety observations under the registered regimens, while its design and reporting limit comparative conclusions.
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 is the absence of a randomized control group. The registry labels allocation as non-randomized and the model as single-group. Consequently, the dose cohorts are descriptive groups rather than equivalent arms assigned to support a causal comparison. Differences in their adverse-event counts should not be interpreted as treatment effects.
The cohorts are small, with group sizes of 3, 3, 3, 13, 6, and 3 participants across the listed regimens. Estimates based on small groups can be unstable, and a small observed count does not establish a low underlying risk. The registry does not report confidence intervals for the safety counts, so their statistical precision cannot be assessed from interval estimates.
The treatment regimen also varies in ways that complicate comparisons: the 40 mg/m^2 dose was given using two infusion durations, later cohorts received other doses, and dose modifications were allowed from the 70 mg/m^2 cohort onward. The record describes pharmacokinetic information as the basis for repeating the 40 mg/m^2 dose with a 1-hour infusion, but it does not report a randomized evaluation of infusion duration.
Further limitations include the absence of reported details on missing data, event attribution, follow-up completeness, the sample-size justification, interim analyses, and the statistical analysis plan. The registry does not report death counts. The listed serious-event term percentages do not have an explicit denominator in the record description. These gaps limit interpretation of event patterns, precision, and the relationship between recorded events and treatment.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Tolerability of IC83/LY2603618 Administered After Pemetrexed 500 mg/m2 Every 21 Days in Patients With Cancer — NCT00415636.
- Registry record last updated 2018-10-19; status last verified 2018-03.
- Results first posted 2018-10-19.
- 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.
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18. Record Summary
NCT00415636 is a completed phase 1, non-randomized, unmasked, single-group dose-escalation study sponsored by Eli Lilly and Company. The record reports enrollment of 31 patients with cancer and describes LY2603618 administered after pemetrexed. The LY2603618 regimens include 40 mg/m^2 with either a 4.5-hour or 1-hour infusion, followed by listed cohorts at 70 mg/m^2, 105 mg/m^2, 150 mg/m^2, and 195 mg/m^2.
The primary outcome is the number of participants with adverse events from baseline up to 24 months. Safety summaries report serious and other non-serious adverse-event participant counts by regimen. The record also names pharmacokinetic measures and best overall response as secondary outcomes. It lists 0 analyses. A randomized control comparison, confidence intervals, missing-data methods, multiplicity strategy, and statistical analysis plan are not reported in the registry record. The posted safety counts are descriptive and do not establish causal differences between regimens.