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 Reacquisition of Radioactive Iodine (RAI) Uptake of RAI-Refractory Metastatic Thyroid Cancers by Pretreatment With the Selective MEK Inhibitor AZD6244 (NCT00970359), a na na study. The primary outcome is Number of Patients Whose Tumor(s) Acquire an Increased Propensity for Iodine Uptake as Detected on Iodine-124 Positron Emission Tomography Scan.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00970359 |
| Phase | NA |
| Condition | Thyroid Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 24 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Memorial Sloan Kettering Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Patients with metastatic thyroid cancer described as refractory to radioactive iodine. The study included patients with and without a BRAF mutation.
Intervention
AZD6244, also identified as selumetinib, taken orally twice daily for 4 weeks.
Comparator
There was no separate comparator group. The study used a single-group design, so it does not provide a like-for-like control comparison.
Primary question
How many patients had tumors with increased iodine uptake detected by iodine-124 positron emission tomography after treatment?
The study was intended to assess whether pretreatment with AZD6244 could increase radioactive iodine uptake in metastatic thyroid cancers that had been resistant to radioactive iodine therapy. Iodine-124 was used to assess uptake through lesional dosimetry. The registry summary describes iodine-124 as allowing measurement of radioactivity entering tumor cells; it distinguishes this imaging approach from iodine-131 treatment.
The investigators also planned to examine whether BRAF mutation status was associated with reacquisition of uptake. That is a question about whether response patterns might differ by a tumor characteristic, not a randomized comparison of treatments. The registry record does not report the primary endpoint result or a result by BRAF status. It therefore does not establish how often increased uptake occurred or whether any observed pattern differed by mutation status.
3. Trial Design
This was a completed pilot study listed as phase NA, with a single-group model and no masking. Allocation is listed as NA. The registry record gives enrollment as 24 and identifies thyroid cancer as the condition. The study start is recorded as 2009-09 and primary completion as 2013-04.
Patients received selumetinib, identified elsewhere in the record as AZD6244, orally twice daily for 4 weeks. Within 1 month, patients with adequate radioactive iodine uptake could receive iodine-131 according to standard of care and continue selumetinib until 2 days following iodine-131. This conditional treatment description does not establish how many patients met the uptake criterion or received iodine-131; those counts are not reported in the registry record.
The design has no separate control group. Its primary question concerns the number of patients whose tumors acquired increased iodine uptake as detected on an iodine-124 positron emission tomography scan, with a stated timeframe of 2 years. The registry record also lists change in serum thyroglobulin levels after treatment with iodine-131 as a secondary outcome. The recorded information does not give results for either outcome.
The record describes the study as completed, but completion status does not by itself provide evidence about the endpoint result, the completeness of follow-up, or the precision of an estimate. Details such as eligibility criteria, the analysis population, and the statistical analysis plan 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
| Stage | AZD6244 |
|---|---|
| STARTED | 24 |
| COMPLETED | 20 |
| NOT COMPLETED | 4 |
Reasons for not completing this period:
| Reason | AZD6244 |
|---|---|
| Not Treated | 4 |
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 | AZD6244 |
|---|---|---|
| Participants analysed | 24 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 14 |
| Age, Categorical: >=65 years | Participants | 10 |
| Sex: Female, Male: Female | Participants | 10 |
| Sex: Female, Male: Male | Participants | 14 |
| Region of Enrollment: United States | participants | 24 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Patients Whose Tumor(s) Acquire an Increased Propensity for Iodine Uptake as Detected on Iodine-124 Positron Emission Tomography Scan, measured over 2 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of patients whose tumor or tumors acquired an increased propensity for iodine uptake, detected with an iodine-124 positron emission tomography scan. The registry lists the unit as participants and gives a timeframe of 2 years. This is a binary outcome at the participant level: a participant either meets the specified uptake criterion or does not, although the operational definition of increased propensity is not reported in the registry record.
In general, an uptake endpoint addresses whether tumors can take up iodine after pretreatment, a property relevant to the study’s rationale. Iodine-124 was used for imaging and lesional dosimetry to assess uptake; the record’s summary distinguishes this measurement from iodine-131 treatment. A count of participants meeting the endpoint can describe how often the specified finding occurred in the study group. To interpret that count as a rate, the analyzed population and its denominator must also be clear.
The registry record does not report the primary endpoint count, the number analyzed, or a confidence interval. As a result, the recorded information does not establish the observed frequency or how precisely it was estimated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a pilot study designed to observe whether metastatic thyroid tumors that were resistant to radioactive iodine acquired increased uptake after AZD6244 pretreatment. Its primary endpoint is a participant count based on iodine-124 imaging. However, the primary outcome result is not reported in the registry record. The central descriptive finding—the number of patients meeting the uptake endpoint—is therefore unavailable, as are an estimate of its uncertainty and an assessment of how complete the endpoint data were.
This absence limits interpretation more than the study’s completed status resolves it. Completion indicates that the study reached a recorded status, not that the registry contains the outcome data needed to evaluate the primary question. Neither a positive nor a negative conclusion about the frequency of reacquired uptake can be drawn from the recorded primary outcome information.
The single-group design is also important. Without a separate control group, an observed change after treatment, if reported, would describe what happened in the treated group; it would not by itself distinguish the effect of AZD6244 from other explanations. The record does not report an adjusted or comparative estimate, and the listed allocation is NA. The design is not a randomized comparison.
The registry summary identifies BRAF mutation status as a feature the investigators intended to examine. But no results by mutation status are reported. It is not possible to determine from the registry record whether uptake differed according to BRAF status, or how precisely any such difference might have been estimated. The listed secondary outcome, change in serum thyroglobulin levels after iodine-131, also has no reported result in the registry record recorded for the study.
Safety information is reported separately from the primary efficacy endpoint. For the AZD6244 group, the record lists 2 participants affected by serious adverse events and 11 affected by other adverse events, with 24 at risk in each category. It also lists gastric ulcer and myelodysplastic syndrome among the leading serious adverse event terms, each at 4.2%. These safety counts do not answer the uptake question and do not create a control comparison. The record does not report deaths.
Overall, the available record describes the question, treatment, design, and some safety counts, but not the primary or secondary outcome findings. Any interpretation should therefore remain limited to the study’s stated aims and recorded design rather than infer an outcome from its completion or enrollment.
9. Statistical Methods Explained
What does a participant count convey?
For a binary endpoint, each participant is classified according to whether the defined event occurred. The primary outcome in this study is framed as the number of patients whose tumors had increased iodine uptake detected by iodine-124 imaging. In general, such a count describes the observed event frequency in the analyzed group. It is not, by itself, a complete estimate of a rate: interpretation also requires a clear denominator and information about which participants were included in the analysis.
The record lists enrollment as 24, but does not report the number analyzed for the primary endpoint, the number meeting the endpoint, or how missing endpoint assessments were handled. Enrollment cannot automatically be treated as the analysis denominator. Without those details, the primary endpoint cannot be reconstructed from the registry record.
Why does a single-group design matter?
In general, a single-group study can describe outcomes observed after an intervention, but it does not directly estimate the difference between that intervention and a concurrent control treatment. A within-group observation may be affected by factors other than the intervention, including changes over time or differences in who has an outcome assessment. A control group can help address some of these issues when designed and analyzed appropriately. This study is recorded as single-group, and no separate comparator group is described.
The registry lists allocation as NA and masking as NONE. These entries do not describe a randomized, masked comparison. The record does not report a statistical plan, details of any adjustment, or a prespecified method for evaluating changes in uptake. Those details should not be inferred from the study’s stated aim.
What would an uncertainty interval mean?
In general, a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical model and procedure. For a binary endpoint, the interval would convey how imprecisely the observed event frequency is estimated, given the analyzed participants. It does not account automatically for every source of uncertainty, such as missing outcomes, measurement choices, or selection into the analyzed group. The registry record does not report a primary endpoint estimate or confidence interval, so no numerical precision assessment is available.
Over-dispersion is a general concern when observed variation exceeds what a chosen statistical model expects. It can make standard errors too small if the model assumes less variability than the data contain. The recorded primary endpoint is a participant count, and no model-based analysis or dispersion estimate is reported; over-dispersion cannot be evaluated from the registry record.
How should planning illustrations be understood?
The record describes sample-size planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not a report of the study’s own design justification. The record does not report the trial’s sample-size justification.
The illustrations use a two-arm planning framework, whereas this study is recorded as single-group. They should therefore not be read as evidence that this trial enrolled a control arm or as a description of its actual allocation. In general, planning estimates depend on their assumptions about effect size, variability, allocation, and statistical procedure; changing those assumptions can change the sample size required. A planning illustration does not show the probability that this completed study detected an effect, and it is not observed power. The registry record does not report an interim analysis plan or the trial’s statistical analysis plan.
What can the recorded safety counts establish?
In general, an adverse-event count is a descriptive summary for the population and event definitions used in the record. A count of affected participants is not necessarily the same as a count of event episodes, since a participant may experience more than one event. The registry record lists the number at risk and the number affected for serious and other adverse events, but does not provide further detail about event timing, duration, severity grading, attribution, or overlap between categories. Those matters cannot be resolved by statistical interpretation alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary endpoint and a secondary outcome involving change in serum thyroglobulin levels after iodine-131. It also describes an intended examination of BRAF mutation status. These are distinct questions, but the record does not report how many statistical tests were planned, whether outcomes or subgroup analyses were ordered in advance, or how multiplicity was addressed. A method for controlling false-positive findings should not be assumed.
Multiplicity is a general issue when several outcomes, time points, subgroups, or statistical tests are considered: the chance of at least one apparently notable finding can increase as the number of analyses grows. Whether and how that concern applies depends on the prespecified analysis plan and the reported results. Neither is available in the registry information summarized for this study.
Missing-data handling is also not reported. The registry does not state how many participants had an interpretable iodine-124 scan, whether any primary endpoint assessments were missing, or how missing assessments were treated. It likewise does not describe missingness for the secondary outcome. Missingness can affect both the denominator and the interpretation of a participant count; no imputation or sensitivity analysis should be presumed.
The analysis population is not reported in the registry record. Enrollment is recorded as 24, but the record does not establish which participants were included in each outcome analysis or whether all enrolled participants were followed to the relevant assessment. The statistical analysis plan, including any interim analyses, is 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 |
|---|---|---|---|
| AZD6244 | 2 | 24 | 8.3% |
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 |
|---|---|
| AZD6244 | 11 of 24 |
Most frequent serious adverse event terms
| Event term | Organ system | AZD6244 |
|---|---|---|
| Gastric ulcer | Gastrointestinal disorders | 1 of 24 |
| Myelodysplastic syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 24 |
Most frequent non-serious adverse event terms
| Event term | Organ system | AZD6244 |
|---|---|---|
| Hypertension | Vascular disorders | 5 of 24 |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 4 of 24 |
| Rash acneiform | Skin and subcutaneous tissue disorders | 3 of 24 |
| Hyperglycemia | Metabolism and nutrition disorders | 2 of 24 |
| Hypocalcemia | Metabolism and nutrition disorders | 2 of 24 |
| Blood bilirubin increased | Investigations | 1 of 24 |
| Creatinine increased | Investigations | 1 of 24 |
| Hyperkalemia | Metabolism and nutrition disorders | 1 of 24 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 1 of 24 |
| Palpitations | Cardiac disorders | 1 of 24 |
Serious events with the highest arm-level rate: gastric ulcer (4.2%), myelodysplastic syndrome (4.2%).
For AZD6244, the registry record lists 24 participants at risk for serious adverse events and 2 affected. It also lists 24 at risk for other adverse events and 11 affected. These are separate summaries; the record does not explain whether participants could be included in both categories. The counts describe affected participants, not necessarily the total number of event episodes.
Gastric ulcer and myelodysplastic syndrome are each listed at 4.2% among the leading serious adverse event terms. The record does not give additional details such as event timing, duration, grading, or attribution. Deaths are not reported in the registry record.
These figures are descriptive safety information for the recorded group. With no separate comparator group, they do not provide a like-for-like estimate of how event frequency would compare under another treatment or without treatment. They should also be read separately from the primary endpoint, which concerns iodine uptake and has no reported result in the registry record.
12. What the Result Does, and Does Not, Mean
The study addresses a specific measurement question: whether metastatic thyroid tumors resistant to radioactive iodine show increased iodine uptake after AZD6244 pretreatment, as assessed by iodine-124 imaging. The record gives the treatment schedule and identifies the intended primary endpoint. It does not report the primary endpoint count or its statistical uncertainty, so it cannot establish the frequency of reacquired uptake in the study group.
Even if a result were available, a single-group design would limit what could be concluded about cause. In general, an outcome observed after treatment does not, on its own, show what would have happened to comparable patients without that treatment. The registry record does not describe a separate control group or a randomized comparison. It also does not report results by BRAF status, despite describing that feature as an intended line of investigation.
The listed secondary outcome, change in serum thyroglobulin levels after iodine-131, is not accompanied by a result in the registry information available for this analysis. Nor does the primary endpoint entry include a reported number analyzed or a confidence interval. These omissions prevent assessment of both the observed outcome and its precision.
The safety record contains counts and leading serious adverse event terms, but without a comparator these cannot establish comparative safety. They also do not resolve details that are not reported, such as event timing or attribution. The study’s completed status and recorded enrollment do not fill these gaps.
Accordingly, the registry record supports a description of the study’s purpose, design, intervention, and some safety information. It does not support a conclusion about the primary uptake outcome, the relationship between BRAF status and uptake, or the comparative effects of AZD6244.
13. Why This Trial Matters Statistically
This trial illustrates how the scientific question and the design shape the meaning of a result. The investigators focused on a measurable imaging outcome: whether tumors acquired increased iodine uptake after AZD6244 pretreatment. Using iodine-124 for lesional dosimetry provides a way to assess uptake as described in the registry summary, while the record distinguishes that assessment from iodine-131 treatment.
Statistically, the primary outcome is a participant count in a single-group pilot study. Such a result would be descriptive of the participants analyzed. Without a comparator, it would not directly quantify a difference between AZD6244 and another approach. A clear denominator and an uncertainty estimate would also be needed to judge the stability and precision of the observed frequency.
The registry record makes these interpretation needs especially visible because it describes the endpoint but does not report its result, analysis population, or uncertainty. It also identifies a planned interest in BRAF mutation status without reporting subgroup findings. The difference between a stated research question and a reported statistical result matters: the former explains what investigators set out to learn, while the latter is needed to assess what the data showed.
The sample-size planning description offers another general lesson. Planning illustrations based on an observed effect and a two-arm framework are assumptions for planning, not proof that a study was designed or analyzed in that way. Here, the recorded study model is single-group. Keeping planning assumptions distinct from the actual design prevents misreading hypothetical calculations as trial findings.
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 central limitation for interpreting this study’s results is that the registry record does not report the primary endpoint finding. It also does not report the number analyzed, a confidence interval, or a detailed definition of the increased-uptake criterion. The outcome’s stated 2 years timeframe does not by itself establish when assessments occurred for individual participants or how complete follow-up was.
The single-group design has no separate comparator. Consequently, the design does not provide a direct treatment contrast. The record lists allocation as NA and masking as NONE; it does not report a statistical analysis plan, adjustment strategy, or interim analysis details.
The investigators’ intended interest in BRAF mutation status is described, but subgroup results are not reported. The secondary outcome concerning serum thyroglobulin levels after iodine-131 is also listed without a reported result. The record does not describe missing-data methods, analysis populations, or how multiple outcomes or subgroup analyses were handled.
The safety entry supplies counts for affected participants and leading serious event terms, but does not report event timing, attribution, or further clinical detail. Deaths are not reported in the registry record. These limitations mean that the available information supports a description of design and recorded safety counts, not a complete evaluation of efficacy, precision, or comparative safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Reacquisition of Radioactive Iodine (RAI) Uptake of RAI-Refractory Metastatic Thyroid Cancers by Pretreatment With the Selective MEK Inhibitor AZD6244 — NCT00970359.
- Registry record last updated 2017-04-12; status last verified 2017-03.
- Results first posted 2017-04-12.
- 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
NCT00970359 is a completed, single-group pilot study of AZD6244, also identified as selumetinib, in metastatic thyroid cancer described as refractory to radioactive iodine. Enrollment is recorded as 24. The study is listed as phase NA, with no masking and allocation NA.
Participants received selumetinib orally twice daily for 4 weeks. Those with adequate uptake could receive iodine-131 within 1 month and continue selumetinib until 2 days following iodine-131. The primary endpoint concerns the number of patients whose tumors acquired increased iodine uptake detected by iodine-124 imaging, with a timeframe of 2 years.
The registry record does not report the primary endpoint result, the secondary outcome result, an analysis population, or statistical analysis details. Safety information lists 2 participants affected by serious adverse events and 11 affected by other adverse events, with 24 at risk in each category. Gastric ulcer and myelodysplastic syndrome are each listed at 4.2% among the leading serious event terms.