Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436 (NCT01534897), a na na study. The primary outcome is Increased Radioiodine Uptake.

2. Clinical Question

In general, this type of question concerns a biological response observed after treatment begins. A change in uptake can be recorded as a participant-level outcome, but an observed response in a single group does not establish what would have happened to the same participants without the intervention. The record also describes safety and other clinical outcomes as study interests, but does not report their full results.

3. Trial Design

The registry describes a completed, single-group study sponsored by Massachusetts General Hospital. It lists enrollment of 10 participants, phase NA, allocation NA, and no masking. The start is recorded as 2012-07 and primary completion as 2014-03. The condition listed is papillary thyroid carcinoma. These registry entries identify the broad design and timeline, but do not establish the number of participants who completed treatment or contributed data to each outcome.

Participants received GSK2118436, also identified in the arm description as dabrafenib. The regimen was 150 mg by mouth twice per day for 28 days, with continuation to day 42 if the day 25 Iodine-131 scan showed new uptake. Participants with new uptake who continued dabrafenib to day 42 were to receive a treatment dose of 150 mCi of Iodine-131 on day 37. This conditional treatment description is part of the registry record; details of adherence, deviations, or how many participants followed each path are not reported.

The primary outcome was increased radioiodine uptake, assessed 25 days after starting dabrafenib. The study description says uptake was assessed by whole body scan and areas of interest identified by nuclear medicine physicians. Listed secondary outcomes concern adverse events, change in tumor size, completion with minimal delays and no dose reductions, and change in thyroglobulin level. The registry lists five outcome measures overall, but does not report results for these outcomes in the record used for this analysis.

A single-group design can describe outcomes observed among participants receiving the study regimen. Without a concurrent comparison group, it cannot separate the effect associated with treatment from other explanations, including the natural course of disease or differences in participants’ circumstances. Randomization and masking are not described as features of this study; the registry lists allocation as NA and masking as none. The rationale, detailed protocol, and 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.

Before assignment: All patients recruited were enrolled, and all patients completed the study.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Increased Radioiodine Uptake, measured over 25 days after start of Dabrafenib (GSK2118436).

The primary endpoint is the number of participants with increased radioiodine uptake in their disease sites while receiving dabrafenib. The registry defines the assessment at 25 days after starting treatment. It specifies a whole body scan and says nuclear medicine physicians identify areas of interest. The endpoint is therefore a participant-level count based on an imaging assessment, rather than a reported continuous measurement of uptake intensity.

In general, uptake is a relevant measurement for a study asking whether disease sites demonstrate a change in radioiodine uptake during treatment. A prespecified time point gives the assessment a shared reference within the study, while a participant count offers a direct description of how many people meet the stated endpoint. The registry record does not report additional operational details, such as a quantitative threshold for increased uptake, how disagreements in image interpretation were handled, or whether all participants had an evaluable scan.

The result for this primary endpoint is not reported in the registry record. The enrollment count alone cannot be used to infer the number with increased uptake, and the conditional treatment description does not establish that any participant met the endpoint. Without the observed endpoint count and an analysis denominator, the frequency of response and its precision cannot be assessed from the posted results. Even if a count were available, a single-group observation would describe the participants studied rather than provide a direct comparison with an alternative treatment or no treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on matching the method to the endpoint, design, and amount of information available. In this study, the primary outcome is a count of participants meeting a binary definition: increased radioiodine uptake or not. The registry record gives the definition and timing but does not report the observed count. The discussion below explains general concepts relevant to this kind of outcome; it does not imply that a particular unreported analysis was performed.

What does a participant count represent?

For a binary endpoint, each participant is classified according to whether the specified event occurred. A count is the number classified as having the event. To interpret that count as a frequency, the analysis also needs a denominator: the number of participants whose endpoint status could be assessed. Enrollment is not automatically the same as the denominator, because participants may lack an assessment or may not meet analysis criteria. In this study, enrollment was 10, but the number assessed for increased uptake and the number with increased uptake are not reported in the registry record.

In general, a confidence interval describes the statistical uncertainty around an estimate, such as the frequency of a binary response. Its width depends on the amount of information and the observed data. A confidence interval is not a guarantee that the true value lies within a particular range, and it does not address limitations such as selection, measurement, or lack of a comparator. No confidence interval for the primary endpoint is reported in the registry record.

What does the single-group design allow?

The registry classifies the model as single group. In a single-group study, outcomes can be described among the participants receiving the intervention, but there is no concurrent group to provide a direct contrast. In general, observing an outcome after treatment does not by itself establish that treatment caused it. A comparison group can help account for changes that might occur over time or from factors other than the intervention. The registry lists allocation as NA and masking as none; random assignment and masking should not be inferred from those entries.

The conditional regimen also matters when defining what is being described. The intervention description specifies continuation to day 42 for participants whose day 25 scan showed new uptake, and an Iodine-131 treatment dose on day 37 for those who continued. The record does not report how many participants followed each route or how adherence was handled in analysis. Without these details, the treatment exposure received by each participant and its relation to outcomes cannot be reconstructed from the registry record.

How should planning calculations be understood?

General sample-size calculations estimate how many participants might be needed under stated assumptions to detect a specified effect with a chosen statistical approach. The registry’s planning illustration is explicitly not the trial’s own design. It uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect described as a stated fraction of the observed effect. The illustrations give participants per arm for non-time-to-event outcomes. Those assumptions do not change the actual study design: this trial was single group and enrolled 10 participants.

These calculations are planning illustrations, not evidence about the probability that the study found an effect. In general, post hoc calculations based on an observed effect should not be described as observed power. They do not substitute for the observed outcome, its uncertainty, or a prespecified design rationale. The registry record does not report the original sample-size justification, and no sample-size illustration can recover the missing primary endpoint result.

Why can event counts be difficult to interpret?

Safety results are counts of participants affected in specified categories. Such counts are useful for describing how many participants were recorded as affected, but they do not necessarily describe how many separate events occurred. General safety interpretation also depends on definitions, event timing, severity, duration, and whether events were considered related to treatment. Those details are not reported for the figures available in the registry record. With a small enrolled group, counts may change noticeably with the outcome of an individual participant; the counts should therefore be read as descriptions of this group, not as stable estimates of risk in a broader population.

What can be said about statistical testing?

The registry record reports no analyses. It does not report a test for the primary outcome, an estimated effect, a p-value, an interval estimate, or an adjustment for multiple outcomes. In general, a p-value addresses how compatible data are with a specified null model under assumptions; it does not measure clinical importance or the probability that a treatment works. An interval estimate communicates precision as well as direction when an effect is defined. Neither kind of result can be interpreted when the relevant outcome data and analysis are absent. The most defensible statistical reading is therefore descriptive: the design and endpoint are stated, some safety counts are listed, and the primary outcome result is not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("GSK2118436")
n      <- c(10)
events <- c(6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  GSK2118436  10  6  60.0  26.2  87.8  31.3  83.2  30.8  83.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary outcome of increased radioiodine uptake and secondary outcomes concerning adverse events, tumor size, study completion with minimal delays and no dose reductions, and thyroglobulin level. Testing or estimating multiple outcomes raises a general multiplicity issue: the chance of at least one apparently notable result can increase when many outcomes are examined. In general, an analysis plan may address this by specifying a primary endpoint, an order for testing, or an adjustment. The registry record does not report whether any such approach was planned or used.

The record reports zero analyses. It does not provide an inferential result for the primary endpoint or the secondary outcomes, and no multiplicity adjustment is reported in the registry record. It is therefore not possible to assess how outcomes were prioritized, whether subgroup or repeated assessments were considered, or whether reported analyses followed a prespecified plan. The detailed statistical analysis plan and any interim analyses are not reported in the registry record.

Missing-data methods and analysis populations are also not reported. The enrollment count is 10, but the registry record does not state how many participants contributed to each outcome, how unavailable scans or measurements were treated, or whether analyses used all enrolled participants or another defined group. These details matter in general because an analysis restricted to participants with available assessments can differ from one that handles missing observations under explicit assumptions. Without the endpoint denominator and missing-data approach, neither the primary outcome frequency nor the potential influence of missing assessments can be evaluated.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for the GSK2118436 group as 0 affected among 10 at risk. For the other adverse event measure, it reports 10 affected among 10 at risk. The record does not report a death count. These are participant counts, not a measure of the total number of separate events, and the category labeled other should not be treated as a complete description of event type or severity.

In general, an at-risk count is the number of participants represented in a safety measure, while the affected count indicates how many had at least one event meeting that measure. The registry record does not specify event timing, duration, severity details for the other adverse events, or attribution to treatment in the information available. A zero count in the serious category means no participant was recorded as affected in that category in this record; it does not establish that serious events are impossible or that the regimen has no safety risks. The small enrolled group also limits how broadly these counts can be generalized.

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

The registry record describes a study asking whether dabrafenib was accompanied by increased radioiodine uptake in disease sites among patients with radioiodine-refractory, BRAF V600E-mutant papillary thyroid carcinoma. It identifies the imaging assessment, the day 25 timeframe, the single-group design, and enrollment of 10. It also reports safety counts for serious and other adverse events. These registry entries provide context for the question and the observations recorded, but the primary endpoint result is not reported in the registry record.

Without the number of participants with increased uptake and the number assessed, the primary outcome cannot be summarized as a frequency or evaluated for statistical precision. The absence of that result is not evidence that uptake did or did not increase. Similarly, no results are reported for the listed secondary outcomes in the registry record. The safety counts are descriptive and do not establish how the treatment compares with another option or what would have happened without it.

The single-group design is a central interpretive constraint. In general, an observed change during treatment can be consistent with a treatment effect, but without a concurrent comparison it cannot isolate treatment as the cause. Other influences and the course of disease remain possible explanations. The record does not report the protocol details or analysis plan needed to assess further design and analysis choices.

Accordingly, the record supports a limited statistical conclusion: it documents a completed study with a defined primary outcome and a small enrolled group, but does not report the primary outcome result. It provides a pair of adverse-event participant counts, which should be read as counts in this study rather than comparative or broadly generalizable risk estimates. The stated endpoint and regimen can inform understanding of what the study set out to examine, but they are not themselves evidence that the intended outcome occurred.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a clearly stated research question and a result that can be evaluated. The registry defines increased radioiodine uptake as the primary endpoint and gives its assessment timing and method. Yet the primary endpoint count is not reported in the registry record. Without an observed count and denominator, readers cannot estimate the response frequency or judge its precision. A well-defined endpoint is essential, but it cannot replace outcome data.

The single-group design also highlights the distinction between observing an outcome and estimating a comparative effect. Participants received dabrafenib under a regimen that included a conditional continuation and Iodine-131 treatment pathway. There is no concurrent comparison arm in the registry record. In general, a single group can describe what occurred among those treated, while a comparative design is needed to estimate differences between treatment strategies under specified assumptions.

The safety figures illustrate why denominators and outcome definitions matter. Counts of participants affected can communicate the number represented in each category, but do not by themselves give event frequency in a broader population, event severity, or treatment attribution. In this record, the serious adverse event count is reported alongside a count for other adverse events, while event-level detail is not available.

Finally, the record does not report analyses, missing-data methods, or a multiplicity approach. These omissions limit the ability to assess precision, robustness, and how the stated outcomes were handled analytically. The statistical lesson is not a judgment about the intervention; it is that study design, outcome definitions, complete reporting, and a suitable comparison all shape what conclusions the data can support.

15. Limitations

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

The enrolled group was 10, and the study had a single-group design. The registry record does not describe a comparator, so outcomes cannot be interpreted as differences relative to another treatment or to no treatment. Masking is listed as none. The record does not report further details about outcome assessment procedures or safeguards against measurement bias beyond stating that whole body scans were used and nuclear medicine physicians identified areas of interest.

The most important reporting limitation is that the primary endpoint result is not reported in the registry record. Neither the number with increased uptake nor the number evaluated is given. Results for the listed secondary outcomes are also not reported in the available record. The adverse-event counts do not include event-level details, and a death count is not reported. These omissions prevent fuller assessment of response, precision, missingness, and safety patterns.

The record does not report the original sample-size justification, statistical analysis plan, analysis populations, methods for handling missing data, or any interim analyses. It also does not report how many participants followed each part of the conditional regimen, including continuation to day 42 or receipt of Iodine-131. These details limit reconstruction of exposure and analysis decisions. The listed phase is NA, which does not provide a phase classification for interpreting the study’s development context. The status is completed, but completion alone does not supply the missing outcome results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Re-differentiation of Radioiodine-Refractory BRAF V600E-mutant Papillary Thyroid Carcinoma With GSK2118436 — NCT01534897.
• Registry record last updated 2017-03-15; status last verified 2017-01.
• Results first posted 2017-03-15.
• 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.

19. Record Summary

NCT01534897 is a completed single-group study sponsored by Massachusetts General Hospital, with enrollment of 10 and no masking. The record lists phase and allocation as NA. It concerns papillary thyroid carcinoma and evaluates GSK2118436, identified in the regimen description as dabrafenib. The stated primary outcome is increased radioiodine uptake 25 days after starting treatment, assessed by whole body scan.

The regimen description specifies 150 mg by mouth twice per day for 28 days, with continuation to day 42 conditional on new uptake at the day 25 scan. Participants continuing to day 42 were to receive 150 mCi of Iodine-131 on day 37. The primary endpoint result and listed secondary outcome results are not reported in the registry record. Safety counts list 0 serious adverse events among 10 at risk and 10 affected for the other adverse event measure among 10 at risk. A death count, statistical analyses, and the detailed analysis plan are not reported in the registry record.