Safety and Efficacy Study of MK0974 in the Acute Migraine (0974-016): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of MK0974 in the Acute Migraine (0974-016) (NCT00432237), a randomized phase 3 study. The primary outcome is Number of Patients Reporting Pain Freedom at 2 Hours Postdose.

2. Clinical Question

The question is about a specific patient-reported outcome at a defined time after treatment of one attack. It is not a measure of every migraine symptom or of longer-term attack prevention. The trial also recorded outcomes concerning sustained pain freedom and total migraine freedom. The registry record does not report the broader clinical context needed to judge how participants were selected beyond the stated analysis population, nor does it report the original rationale for choosing the doses or outcome timing.

3. Trial Design

This was a Phase III, randomized, double-masked, parallel-group, placebo-controlled clinical trial of oral MK0974 for acute migraine with or without aura. The registry record lists an enrollment of 1703 and a completed status. The study start is recorded as 2007-03 and primary completion as 2007-12. Merck Sharp & Dohme LLC is listed as sponsor.

Participants were assigned to MK0974 50 mg, MK0974 150 mg, MK0974 300 mg, or placebo. The arm descriptions specify a single orally administered dose for one moderate-to-severe migraine attack, with an optional second dose. In the 50 mg and 150 mg arms, the optional dose is the same assigned dose; in the 300 mg arm, it may be MK0974 300 mg or placebo. The placebo arm specifies placebo for both the initial and optional dose.

Randomization and double masking are features intended to reduce systematic differences in treatment assignment and expectations. The registry record does not report the randomization procedure, allocation concealment details, or how masking was maintained. It also does not report the original sample-size justification or the planned statistical analysis in enough detail to establish the trial’s full analysis strategy.

The primary outcome population is described as all randomized, treated participants with at least one postdose measurement at or prior to 2 hours. The outcome counts have different denominators across arms, and the record does not explain the reasons for those differences. The primary outcome is a count of participants meeting a binary definition, rather than a continuous measure of symptom change.

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: Participants were assessed, using the protocol inclusion and exclusion criteria, at Visit 1, and if eligible were randomized at that same visit.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized, treated patients who have at least one post-dose measurement at or prior to 2 hours.

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 Number of Patients Reporting Pain Freedom at 2 Hours Postdose, measured over 2 hours post dose.

The primary endpoint counts participants reporting pain freedom at 2 hours postdose. Pain freedom was defined as a change from Grade 2 or Grade 3 migraine severity at baseline to Grade 0, meaning no pain, at 2 hours. Participants recorded headache severity in a diary on a scale where 0 means no pain, 1 mild pain, 2 moderate pain, and 3 severe pain.

This is a binary endpoint: each participant either met the specified pain-freedom definition at the assessment time or did not. Counting participants who meet a defined threshold makes the outcome directly interpretable as the number experiencing that particular result in each group. It also preserves the distinction between reaching no pain and merely having less pain. The endpoint does not describe the size of symptom change among participants who did not reach Grade 0.

The fixed assessment time matters because the endpoint addresses pain status 2 hours after dosing, not pain status throughout the day or across later attacks. Other registry outcomes address sustained pain freedom and total migraine freedom over specified periods, but they are distinct outcomes and should not be treated as interchangeable with the primary measure. The registry record does not report additional details about diary completion, missing observations, or the handling of participants without a qualifying postdose assessment.

7. Results Posted in the Registry

• MK0974 50 mg: 16.5% (29/176) versus 10.7% (39/365) on control; risk difference 5.8 percentage points (95% CI -0.5 to 12.1), risk ratio 1.54 (0.99–2.41); unadjusted two-proportion z-test p = 0.057.
• MK0974 150 mg: 23.2% (88/380) versus 10.7% (39/365) on control; risk difference 12.5 percentage points (95% CI 7.2 to 17.8), risk ratio 2.17 (1.53–3.07); unadjusted two-proportion z-test p = <0.001.
• MK0974 300 mg: 23.8% (88/369) versus 10.7% (39/365) on control; risk difference 13.2 percentage points (95% CI 7.8 to 18.5), risk ratio 2.23 (1.58–3.16); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Patients Who Have Sustained Pain-Freedom From 2 to 24 Hours Postdose

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • MK0974 50 mg: 14.1% (25/177) versus 7.2% (26/363) on control; risk difference 7.0 percentage points (95% CI 1.2 to 12.7), risk ratio 1.97 (1.17–3.31); unadjusted two-proportion z-test p = 0.009.
  • MK0974 150 mg: 16.4% (62/378) versus 7.2% (26/363) on control; risk difference 9.2 percentage points (95% CI 4.7 to 13.8), risk ratio 2.29 (1.48–3.54); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for MK0974 50 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for MK0974 150 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Patients Who Have Total Migraine Freedom 2 to 24 Hours Postdose

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • MK0974 50 mg: 11.3% (20/177) versus 6.3% (23/363) on control; risk difference 5.0 percentage points (95% CI -0.3 to 10.3), risk ratio 1.78 (1.01–3.16); unadjusted two-proportion z-test p = 0.046.
  • MK0974 150 mg: 14.6% (55/378) versus 6.3% (23/363) on control; risk difference 8.2 percentage points (95% CI 3.9 to 12.6), risk ratio 2.30 (1.44–3.66); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between MK0974 50 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for MK0974 150 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Patients Who Have Total Migraine Freedom 2 Hours Postdose

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • MK0974 50 mg: 13.6% (24/176) versus 9.9% (36/365) on control; risk difference 3.8 percentage points (95% CI -2.1 to 9.7), risk ratio 1.38 (0.85–2.24); unadjusted two-proportion z-test p = 0.190.
  • MK0974 150 mg: 20.5% (78/380) versus 9.9% (36/365) on control; risk difference 10.7 percentage points (95% CI 5.6 to 15.7), risk ratio 2.08 (1.44–3.01); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between MK0974 50 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for MK0974 150 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes concern sustained pain freedom from 2 to 24 hours, total migraine freedom from 2 to 24 hours, and total migraine freedom at 2 hours. Across these outcomes, the posted counts and recalculated comparisons generally show a more consistent separation from placebo for the 150 mg and 300 mg groups than for 50 mg. The degree of separation is not identical across endpoints, and the outcomes describe different aspects or durations of symptom status.

This broad pattern is directionally compatible with the primary endpoint’s clearer recalculated comparisons for the 150 mg and 300 mg groups than for 50 mg. It does not make the secondary outcomes interchangeable with the primary endpoint. Sustained pain freedom requires maintaining a result over a later period, while total migraine freedom is a distinct outcome as defined by the registry. The record does not provide further operational definitions for the total migraine-freedom outcomes.

The sponsor’s listed logistic-regression results for the secondary outcomes report p < 0.001 for comparisons involving the 150 mg and 300 mg groups in the posted analyses. Recalculated comparisons also include unadjusted p-values. These should be interpreted cautiously because the registry record lists multiple outcomes and treatment comparisons but does not report a multiplicity-adjustment plan. When many outcomes or contrasts are examined, the chance of at least one small p-value can increase. Without a stated strategy for controlling that risk, unadjusted secondary findings carry less inferential weight than a prespecified primary analysis.

The registry record identifies three posted secondary outcomes, but does not report a complete analysis hierarchy or explain whether any secondary endpoint was confirmatory. The pattern can add context to the primary result, but it should not be used as a collection of independent confirmations.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Patients Who Have Sustained Pain-Freedom From 2 to 24 Hours Postdose
• Number of Patients Who Have Total Migraine Freedom 2 to 24 Hours Postdose
• Number of Patients Who Have Total Migraine Freedom 2 Hours Postdose

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary because it records whether each participant met the pain-freedom definition at 2 hours. The posted arm counts and denominators describe the observed frequency of that outcome in each group. A comparison of those frequencies can be expressed in different ways, each answering a slightly different descriptive question.

What does a risk difference describe?

A risk difference is the event proportion in one group minus the event proportion in the comparison group. It is an absolute contrast on the proportion scale. A positive value in these recalculations means that the observed pain-freedom proportion was higher in the named MK0974 group than in placebo. For example, the recalculated primary risk differences are 0.058 for 50 mg, 0.125 for 150 mg, and 0.132 for 300 mg. Those are unadjusted contrasts calculated from the posted summary statistics, not adjusted estimates from a regression model.

What do the intervals add?

A confidence interval gives a range of effect estimates compatible with the data under the method’s assumptions. It conveys uncertainty about the estimated contrast: a narrower interval indicates greater precision, while a wider interval indicates less precision. An interval spanning zero includes both a positive and a negative risk difference, as well as no difference. For the 50 mg comparison, the recalculated interval ranges from -0.005 to 0.121. The 150 mg and 300 mg intervals range from 0.072 to 0.178 and from 0.078 to 0.185, respectively. These are recalculated intervals; the registry record does not provide a confidence level for these recalculated contrasts. The sponsor-reported analyses list 95% confidence intervals as a nominal level, but do not provide interval limits in the record.

How should p-values be read?

A p-value describes how unusual the observed data, or more extreme data, would be under a null hypothesis and the assumptions of the test. It is not the probability that the null hypothesis is true. The simple recalculation gives p = 0.057 for 50 mg and p < 0.001 for 150 mg and 300 mg. The sponsor’s listed logistic-regression results for 150 mg and 300 mg each report p < 0.001. These p-values arise from different analyses: the recalculations use unadjusted summary statistics, while the sponsor’s listed method is logistic regression.

Why can analysis methods differ?

Logistic regression models the probability of a binary outcome using the log odds scale and can incorporate analysis features specified by the trial’s statistical plan. The registry record identifies logistic regression for the sponsor’s listed comparisons but does not report the model specification, covariates, handling of missing data, or all other details needed to reproduce it. Consequently, the recalculated risk differences and sponsor-reported p-values need not match exactly. The discrepancy flag means the sponsor’s own analysis takes precedence for its intended inferential result.

What does randomization contribute?

In general, random assignment aims to make treatment groups comparable with respect to measured and unmeasured characteristics at the point of assignment. Double masking can reduce influences from treatment knowledge on participants’ reports and study conduct. These design features support interpretation of between-group contrasts, but they do not remove uncertainty from sampling variation or resolve missing outcome information. Details of the randomization process and masking procedures are not reported in the registry record.

Why are counts not the whole analysis?

Counts and denominators let readers understand the observed event frequency, while contrasts and uncertainty intervals describe between-group evidence. The primary analysis population is restricted to randomized, treated participants with at least one postdose measurement at or before 2 hours. How participants lacking measurements were handled is not reported in the registry record. The displayed denominators should therefore be read as outcome-specific analysis counts, not assumed to represent every randomized participant.

What is over-dispersion?

General explanation: over-dispersion occurs when observed variability exceeds what a chosen statistical model assumes. It is a concern for some outcomes and models, especially when variability is more than expected under a simple count distribution. The primary endpoint is a binary participant count, and dispersion is not reported as a measure for this endpoint. The registry record does not describe an over-dispersion assessment or a model that addresses it.

11. Confidence Intervals and Precision

The recalculated risk differences are accompanied by intervals that describe uncertainty around each absolute comparison. For 50 mg, the interval runs from -0.005 to 0.121. Its width reflects meaningful uncertainty about the size and even the direction of the difference. The interval includes zero, so the data are compatible with little or no difference as well as with a positive difference within the stated limits.

For 150 mg, the interval is 0.072 to 0.178; for 300 mg, it is 0.078 to 0.185. Both are above zero, indicating that the corresponding unadjusted recalculated estimates are separated from zero over their interval ranges. The limits still allow a range of plausible effect magnitudes, so the point estimates should not be treated as exact values.

The registry record reports 95% as the confidence-interval level for the listed sponsor analyses, but does not provide sponsor interval limits. The recalculated interval level is not stated in the registry record. The intervals should therefore be identified as recalculated rather than attributed to the sponsor’s logistic-regression analysis.

Precision depends on both the number of observations and the event pattern. The analysis denominators vary across groups, and the registry record does not explain those differences. A confidence interval does not account for every possible source of uncertainty, such as unreported analysis choices or missing-data handling. It quantifies sampling uncertainty under its calculation method; it cannot establish that the endpoint captures every aspect of migraine or that the result applies outside the studied setting.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations express the number of participants per arm for binary outcomes, including the primary endpoint. They are not total-event counts. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each illustration uses an effect equal to the stated fraction of the observed effect. The trial’s own original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the illustrative participants per arm for a design that would have an 80% chance of detecting the specified effect if that effect were the true one, under the stated assumptions. The 90% power column describes the corresponding planning target with a higher chance of detecting that same effect. These are design-planning quantities, not guarantees about a future study’s result.

Rows planning for 100%, 75%, or 50% of the observed effect show how the illustrative requirement changes when the target effect is smaller than the observed estimate. Smaller effects generally require more participants to distinguish them from chance variation at the same significance and power settings. The curve visualizes this planning relationship across the displayed effect assumptions; it does not predict the outcome of a new trial.

This is not observed power. It is a planning illustration calculated from the observed effect and the stated assumptions, not a retrospective measure of whether the completed trial was adequately powered. Because observed effects can be imprecise, the planning figures should not be taken as a definitive sample-size recommendation.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.107; treatment proportion p₁ = 0.165; average p̄ = 0.136.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4845 = 0.9496.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4828 = 0.4063.
4. n = (0.9496 + 0.4063)² / (0.0579)² = 547.9, rounded up to 548 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.106849315068493                          # control proportion
p1 <- 0.164772727272727                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(432237)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 548 (80% power), 734 (90% power)
 75% of observed effect: n per arm = 931 (80% power), 1,246 (90% power)
 50% of observed effect: n per arm = 1,995 (80% power), 2,669 (90% power)
power.prop.test: 547.9 
Simulated power at n = 548 per arm: 0.797 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry record lists sponsor analyses using logistic regression for the comparisons of MK0974 150 mg with placebo and MK0974 300 mg with placebo. Each is reported with p < 0.001 and a 95% confidence-interval level, but the record does not give the sponsor’s estimated effects or interval limits for those comparisons. It does not list a sponsor analysis for the 50 mg comparison among the reported analyses.

The risk differences, intervals, and unadjusted p-values discussed for the three primary comparisons are simple recalculations from posted arm counts and denominators. They are not the sponsor’s model-based results. Differences can arise because the calculations and analysis methods differ; the registry record does not report enough detail about the logistic-regression model to reproduce the sponsor’s analysis.

The record flags a discrepancy. Under that circumstance, the sponsor’s own analysis takes precedence for the trial’s reported inferential result. The recalculations remain useful as a transparent description of the unadjusted contrasts implied by the posted summary counts, but they should not be presented as correcting or replacing the sponsor’s analysis. The available registry results do not permit a detailed reconciliation of the estimates.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when analyses include several outcomes, dose groups, time points, or statistical comparisons. Testing many contrasts can increase the chance of obtaining at least one small p-value even when there is no true effect for any contrast. Common approaches to address this include prespecifying a hierarchy or adjusting the threshold or p-values, but the registry record does not report which approach, if any, was planned for this trial.

The record lists a primary endpoint, three secondary outcomes, and analyses comparing selected dose groups with placebo. It does not report a full statistical analysis plan, the ordering of hypotheses, or whether the secondary analyses were confirmatory or exploratory. The listed p-values should therefore be read as the values reported for those individual comparisons, not assumed to control the overall error rate across all analyses.

The primary analysis population is described as randomized, treated participants with at least one postdose measurement at or prior to 2 hours. This definition clarifies who contributes to the primary endpoint analysis, but does not explain how missing measurements were handled or whether any imputation or sensitivity analysis was used. Reasons for the differences among the arm denominators are not reported in the registry record. The handling of missing data for secondary outcomes is also not reported in the registry record.

The registry record does not describe interim analyses, stopping rules, or whether the analysis population and outcome definitions were finalized before access to unmasked results. Those details cannot be inferred from the completed status or the posted endpoint counts. Without them, readers cannot assess whether all analysis choices were prespecified or how potential deviations were handled.

These reporting gaps do not invalidate the posted counts. They limit how fully the statistical procedures can be evaluated and reproduced. The sponsor-reported logistic-regression p-values and the unadjusted recalculations should remain clearly distinguished, and neither should be interpreted as an across-the-board adjustment for the set of outcomes and comparisons.

16. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: traumatic brain injury (0.3%), hypertension (0.3%).

The registry record lists serious adverse event counts by arm and the corresponding numbers at risk: 0 of 177 for MK0974 50 mg, 1 of 381 for MK0974 150 mg, 0 of 370 for MK0974 300 mg, and 1 of 366 for placebo. These are counts recorded in the registry, not a comparative safety analysis. The record does not provide a statistical comparison or confidence intervals for these figures.

Other adverse event counts are listed as 45 of 177, 69 of 381, 94 of 370, and 77 of 366 for the 50 mg, 150 mg, 300 mg, and placebo groups, respectively. The registry record does not provide enough detail to interpret event severity beyond the separate serious-event category or to establish the relationship of each event to study treatment.

Traumatic Brain Injury and Hypertension are each listed among the top serious adverse event terms at 0.3%. Death counts are not reported in the registry record. Sparse event counts, differing group denominators, and the absence of detailed definitions and comparative analyses limit what can be concluded from these safety figures.

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

The primary outcome is a participant-reported measure of pain status at a particular time after dosing. The posted counts describe how many analyzed participants met the study’s definition of no pain at 2 hours. The recalculated risk differences provide absolute contrasts with placebo, while the intervals convey uncertainty about those contrasts.

For the 150 mg and 300 mg comparisons, the recalculated intervals lie above zero and the unadjusted p-values are p < 0.001. The 50 mg interval includes zero, with an unadjusted p-value of 0.057. The sponsor’s own reported analyses are logistic-regression comparisons for 150 mg and 300 mg, each with p < 0.001; the registry record flags a discrepancy, so those sponsor analyses take precedence for the sponsor’s inferential results. These are statements about the posted endpoint data and analyses, not medical advice or a conclusion about an individual’s care.

A statistical difference does not by itself establish the clinical importance of the difference. The registry record does not provide a threshold for a clinically meaningful difference, nor does the primary endpoint summarize every migraine symptom or the duration of benefit beyond its defined assessment. The secondary outcomes add information about different time periods and definitions, but the record does not report a multiplicity plan that would support treating all secondary comparisons as independent confirmatory evidence.

The study concerns a single acute migraine attack and the outcomes recorded in that setting. It does not establish effects on prevention, repeated attacks, or outcomes not measured in the record. The analysis population excludes randomized, treated participants without at least one qualifying postdose measurement from the primary endpoint definition, and the handling of missing measurements is not reported. Those limits should accompany interpretation of the observed counts and comparisons.

18. Why This Trial Matters Statistically

This trial is statistically informative because it compares three dose groups with a placebo group using a randomized, double-masked, parallel design and a clearly defined binary primary endpoint. The endpoint is based on a patient diary and specifies both the baseline severity requirement and the postdose pain status. That definition makes the outcome interpretable as a count while keeping attention on a concrete assessment time.

The results also illustrate why an effect estimate, an uncertainty interval, and a p-value answer different questions. The recalculated risk differences describe absolute contrasts, their intervals show the range of uncertainty, and the p-values summarize compatibility with a null comparison under the method’s assumptions. For 50 mg, the interval includes zero; for 150 mg and 300 mg, the recalculated intervals are above zero. The sponsor’s listed logistic-regression p-values for 150 mg and 300 mg provide a separate model-based analysis, and the record’s discrepancy flag makes it important not to conflate the two.

Several features make cautious reading especially relevant: multiple dose comparisons and outcomes are listed, multiplicity handling is not reported, and the primary analysis denominators vary. The sponsor’s model details and missing-data procedures are also not reported. These are not reasons to discard the observed results, but they define the limits of what can be reconstructed from the registry record.

The planning illustrations further show how required sample size depends on the effect targeted and the design assumptions. They use the observed effect as a planning input and are not the trial’s original design rationale. Distinguishing that illustration from the completed trial’s evidence prevents retrospective power language from being mistaken for proof of adequacy.

19. 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 registry record contains limited information about participant characteristics beyond the migraine condition and the primary analysis population. It does not report eligibility criteria in detail, baseline comparability, recruitment setting, or the reasons participants were excluded from particular outcome denominators. As a result, readers cannot fully assess how representative the analyzed participants were or why arm-specific analysis counts differ.

The record identifies logistic regression for selected sponsor comparisons but does not report the model specification, covariates, handling of missing outcomes, or other details needed to reproduce those analyses. It also does not report the confidence-interval limits for the sponsor results. The simple recalculations are unadjusted and should not be treated as equivalent to the sponsor’s analysis, especially given the discrepancy flag.

The primary outcome is a diary-based measure at 2 hours. Diary completion procedures, missing-data handling, and sensitivity analyses are not reported in the registry record. The record does not provide a clinically meaningful threshold for interpreting the absolute contrasts. The total migraine-freedom outcome definitions are also not detailed beyond their names and assessment periods.

Multiple treatment comparisons and secondary outcomes are listed, but multiplicity procedures and an analysis hierarchy are not reported. Interim analyses, stopping rules, and the original sample-size rationale are not reported in the registry record. Safety information is presented as counts, with no comparative inferential analysis or death counts. These gaps restrict interpretation and reproducibility without changing what the posted counts themselves state.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of MK0974 in the Acute Migraine (0974-016) — NCT00432237.
• Registry record last updated 2015-07-03; status last verified 2015-06.
• Results first posted 2010-12-06.
• 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.

23. Record Summary

NCT00432237 is a completed Phase III, randomized, double-masked, parallel, placebo-controlled study of oral MK0974 for acute migraine with or without aura. The registry record lists 1703 enrolled participants and four groups: MK0974 50 mg, 150 mg, 300 mg, and placebo. The primary endpoint is the number of participants reporting pain freedom at 2 hours postdose.

The posted primary counts are 29 of 176, 88 of 380, 88 of 369, and 39 of 365 for the respective groups. Simple unadjusted risk-difference recalculations show different levels of precision across dose comparisons. Sponsor-reported logistic-regression analyses are listed for 150 mg and 300 mg versus placebo, each with p < 0.001. Because the record flags a discrepancy, the sponsor’s own analysis takes precedence.

The registry lists three secondary outcomes and adverse event counts. Multiplicity handling, missing-data procedures, detailed model specifications, and the original sample-size rationale are not reported in the registry record.