A Study in Indian Postmenopausal Women With Osteoporosis to Evaluate the Efficacy and Safety of Denosumab: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study in Indian Postmenopausal Women With Osteoporosis to Evaluate the Efficacy and Safety of Denosumab (NCT01495000), a randomized phase 3 study. The primary outcome is Mean Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 6.

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter Phase 3 study of denosumab in Indian postmenopausal women with osteoporosis. The registry lists enrollment of 250 and a completed status. The recorded study start was 2012-01 and primary completion was 2013-02. GlaxoSmithKline is listed as the sponsor.

Participants were assigned to denosumab 60 mg or placebo, each given as a single subcutaneous injection at the start of the 6-month double-blind treatment. The parallel-group design means the treatment groups were followed as separate groups rather than participants crossing from one treatment to another. Double masking means the registry identifies the study as blinded to two parties, but it does not name those parties or describe the practical masking procedures.

The primary outcome was mean percent change from Baseline in lumbar-spine BMD at Month 6. The registry describes an ANCOVA analysis with treatment and baseline BMD as a continuous covariate. The analysis population was defined by receipt of one dose, baseline and post-baseline efficacy measurement, and, for the reported primary endpoint, BMD values at both Baseline and Month 6. The exact number included under every aspect of that population is not reported in the registry record.

Other listed outcomes include BMD at hip sites, bone-turnover markers, adverse events, vital signs, laboratory measurements, and changes in blood measures. The registry record does not report the original sample-size justification, the full sequence of randomization procedures, or detailed masking procedures. Those details should not be inferred from the design labels alone.

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: The study consisted of a Screening Phase of up to 2.5 months and a 6-month Double-blind Treatment Phase. A total of 551 participants (par.) were screened; 303 par. were screen failures, and 250 par. were randomized (2 par. were considered to be screen failures; however, these par. were randomized, 1 to each treatment group).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat Efficacy (ITTE) Population: all randomized participants who received one dose of study medication, and who had a Baseline measure and at least one post-Baseline efficacy measure during the Double-blind Treatment Phase. Only participants with BMD values at both Baseline and Month 6 were analyzed.

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 Mean Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 6, measured over Baseline and Month 6.

The primary endpoint is the mean percent change from Baseline in bone mineral density at the lumbar spine at Month 6. BMD was measured with a dual-energy x-ray absorptiometry scanner. The registry defines the percent change using the Month 6 value and Baseline value, expressed relative to Baseline. The reported group summaries are least-squares means, with standard errors as their dispersion measure.

Lumbar-spine BMD is the endpoint chosen to address the study’s stated efficacy question: whether denosumab changes BMD at this site over the 6-month treatment period compared with placebo. A change-from-baseline measure focuses on how measurements at follow-up differ from each participant’s starting measurement, while the percent scale expresses that change relative to the baseline value. The registry does not provide a threshold for deciding what size of change would be clinically important.

The endpoint is a measurement of BMD, not a direct measure of fractures, symptoms, or quality of life. A difference in this outcome therefore describes the reported BMD comparison; by itself, it does not establish the magnitude of any effect on outcomes that were not measured as the primary endpoint.

7. Results Posted in the Registry

• Denosumab 60 mg: mean 4.26 versus 1.20 on control; difference 3.06 (95% CI 1.93 to 4.19), standardized effect d = 0.74; 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.

Change From Baseline in Hematocrit at Month 6

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Denosumab 60 mg: mean 0.00 versus 0.00 on control; difference 0.00 (95% CI -0.01 to 0.01), standardized effect d = 0.00; z-test p = 1.000.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Denosumab 60 mg and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in Mean Corpuscle Hemoglobin at Month 6

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Denosumab 60 mg: mean 0.41 versus 0.26 on control; difference 0.15 (95% CI -0.15 to 0.44), standardized effect d = 0.13; z-test p = 0.325.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Denosumab 60 mg and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in Mean Corpuscular Volume at Month 6

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Denosumab 60 mg: mean 0.62 versus 0.33 on control; difference 0.30 (95% CI -0.58 to 1.17), standardized effect d = 0.09; z-test p = 0.508.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Denosumab 60 mg and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes span several kinds of information: BMD at other skeletal sites, bone-turnover markers, adverse events, vital signs, laboratory findings, and changes in blood measures. That breadth can help describe whether the primary result sits alongside changes in related measurements and whether the study recorded safety or laboratory observations. The secondary outcomes are not all measures of the same underlying quantity, so a single overall direction should not be assigned to them.

The registry lists 17 secondary outcomes, and the posted numerical summaries cover only a subset of those outcomes. The available secondary comparisons include hematocrit, mean corpuscle hemoglobin, and mean corpuscular volume. Their estimates and uncertainty should be read in their own units and with the methods attached to each outcome, rather than combined into one summary claim. The registry’s secondary outcome descriptions also include outcomes for which the corresponding numerical results are not reported in the registry record.

These outcomes provide context for, but do not independently redefine, the primary lumbar-spine BMD result. Some are biological measurements, while others are safety or laboratory observations. A secondary pattern that is consistent with the primary endpoint could add context, but it would not by itself establish a clinical effect on outcomes that were not measured as primary endpoints.

Unadjusted secondary comparisons carry less weight as confirmatory evidence when many outcomes are examined. In general, the more comparisons made, the greater the opportunity for chance findings unless the analysis plan accounts for multiplicity. Whether a multiplicity procedure, testing hierarchy, or prespecified prioritization was used is not reported in the registry record. The secondary findings should therefore be interpreted cautiously and in relation to their estimates, confidence intervals, and measurement context, not treated as a collection of definitive tests.

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

• Mean Percent Change From Baseline in BMD at the Total Hip, Femoral Neck, and Trochanter at Month 6
• Median Percent Change From Baseline in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) and Serum Procollagen Type IN Propeptide (s-PINP) Markers at Months 1, 3, and 6
• Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE)
• Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Months 1, 3, and 6
• Number of Participants With the Indicated Laboratory Parameter Values of Potential Clinical Concern at Month 6
• Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 6
• Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin Concentration (Conc.), and Total Protein at Month 6
• Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Month 6

9. Statistical Interpretation

10. Statistical Methods Explained

What does the primary estimate represent?

The primary endpoint is a continuous measure: percent change in lumbar-spine BMD from Baseline to Month 6. The registry reports least-squares means for the treatment groups. In general, a least-squares mean is a model-based group estimate, rather than simply a raw arithmetic average. Here, the registry says the ANCOVA model included treatment and baseline lumbar-spine BMD as a continuous covariate. The model therefore estimates the treatment comparison while accounting for the recorded baseline BMD measure.

The sponsor reports a mean difference in final values of 3.05. Its 95% confidence interval is 1.91 to 4.19, and its reported p-value is < 0.001. The posted group summaries also permit a simple unadjusted recalculation: the mean difference is 3.06, with a 95% confidence interval of 1.929 to 4.191 and p < 0.001. This recalculation is not a replacement for the sponsor’s ANCOVA. It is a separate comparison based on the summary statistics, without the stated baseline adjustment.

What does ANCOVA do?

In general, analysis of covariance (ANCOVA) compares groups while including a baseline measurement as a covariate. This can account statistically for differences in baseline values and may improve precision when baseline and follow-up measurements are related. The registry identifies treatment and baseline BMD as model terms. The full model specification, including any other terms or details of assumptions, is not reported in the registry record.

Adjustment does not make the comparison immune to bias or missing data. Interpretation still depends on how participants entered the analysis and on whether the model is appropriate for the data. The registry’s stated efficacy population requires receipt of a dose and available efficacy measurements, and the primary description calls for BMD values at both Baseline and Month 6. The detailed handling of missing values is not reported in the registry record.

How should a confidence interval be read?

In general, a confidence interval expresses uncertainty around an estimated effect under the analysis assumptions. It gives a range of values compatible with the data and method at the stated confidence level; it is not a guarantee that the true effect lies in that interval. For the sponsor’s result, the reported interval is 1.91 to 4.19 at the 95% confidence level. For the unadjusted recalculation, the interval is 1.929 to 4.191. Their proximity reflects that the two estimated comparisons are similar, while the methods remain distinct.

What does the p-value tell the reader?

In general, a p-value describes how unusual data at least as incompatible with a null comparison would be if that null model and its assumptions were correct. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. The sponsor reports p < 0.001 for its ANCOVA analysis; the unadjusted recalculation gives p < 0.001. These values address statistical evidence for a group difference under their respective analyses, not whether the difference matters to patients.

Why can variability matter?

Continuous outcomes vary among participants. The primary group summaries report standard errors, which describe uncertainty in the estimated group means rather than the spread of individual BMD changes. In general, more variability among individual measurements can make an estimate less precise, while larger analysis groups can improve precision, all else being equal. The registry does not provide individual-level data, so the spread of participant-level primary changes cannot be reconstructed from these summaries alone.

What is the role of the other analyses?

The registry lists secondary outcomes covering additional BMD sites, bone-turnover markers, safety events, vital signs, laboratory measures, and blood measurements. These outcomes broaden the set of questions explored but do not alter the definition of the primary endpoint. In general, examining many outcomes increases the chance that some results will appear notable by chance. Whether the trial used a multiplicity adjustment, a prespecified testing hierarchy, or another procedure is not reported in the registry record. Consequently, secondary comparisons should be read as supporting or exploratory evidence rather than as a set of equally definitive confirmations.

11. Confidence Intervals and Precision

The sponsor’s primary ANCOVA estimate is a mean difference of 3.05, with a 95% confidence interval from 1.91 to 4.19. The unadjusted recalculation is 3.06, with a 95% confidence interval from 1.929 to 4.191. Both intervals are entirely above zero. Their widths show that the estimated difference is not known exactly; values across each interval remain compatible with the corresponding analysis and its assumptions.

In general, a confidence interval combines information about the observed estimate and its uncertainty. A narrower interval indicates greater precision for the same kind of estimate and confidence level, while a wider interval indicates less precision. The interval does not include uncertainty about every possible source of bias, departures from model assumptions, or differences between the trial population and other populations. Those issues require separate consideration.

The sponsor’s result comes from ANCOVA, while the recalculation uses posted summary statistics and is unadjusted. The intervals are close, but they should not be treated as interchangeable outputs from one method. The sponsor’s analysis is the registry’s reported analysis. The recalculation is useful as a transparent check of the broad result from the group summaries, not as a substitute for the model-based analysis.

The confidence intervals concern the primary BMD comparison, not clinical importance. The registry record does not report a threshold that would define a meaningful difference in lumbar-spine BMD, and the interval cannot supply that threshold. It also does not quantify effects on outcomes outside the primary endpoint. Precision in estimating this particular difference should therefore be distinguished from certainty about wider clinical implications.

The reported standard errors for the group summaries are 0.413 for denosumab and 0.403 for placebo. Standard errors describe precision of the estimated means, not the range of individual responses. They do not, on their own, reveal how much participant-level changes varied or how many people experienced a particular response.

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 figures are planning illustrations based on the observed primary effect, not the original trial’s design calculations. They assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is set at the stated fraction of the observed effect. The original study’s own sample-size assumptions and justification are not reported in the registry record.

For each effect scenario, the 80% power column gives the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting an effect of that size under its assumptions. The 90% power column gives the corresponding number of participants per arm for a higher chance of detection. These are prospective planning quantities, not descriptions of what happened in the completed trial.

The rows compare planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. Smaller effects are harder to distinguish from random variation, so they require more participants per arm under the same assumptions. The figures should be read as conditional illustrations: changing the assumed effect or planning assumptions would change the resulting sample-size estimates. For this continuous primary outcome, the values are participants per arm, not total events.

These figures are not observed power. Observed power is not an informative substitute for reading the estimate and its confidence interval after a study has finished. The interval and estimate describe the uncertainty and size of the observed comparison directly; the planning values instead illustrate sample requirements for hypothetical future studies under the stated assumptions.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 3.060; pooled standard deviation σ = 4.130.
2. n = 2 × (1.96 + 0.842)² × 4.130² / 3.060² = 28.6, rounded up to 29 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
delta <- 3.06                      # observed difference in means
sigma <- 4.12975468921623                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1495000)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 29 (80% power), 39 (90% power)
 75% of observed effect: n per arm = 51 (80% power), 69 (90% power)
 50% of observed effect: n per arm = 115 (80% power), 154 (90% power)
power.t.test: 29.6 
Simulated power at n = 29 per arm: 0.790 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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 sponsor reports an ANCOVA mean difference in final values of 3.05, with a 95% confidence interval from 1.91 to 4.19 and p < 0.001. The ANCOVA model is described as including treatment and baseline lumbar-spine BMD as a continuous covariate. This is the registry’s own analysis and should be treated as the primary reported inferential result.

A simple unadjusted recalculation from the posted group summaries gives a mean difference of 3.06, a 95% confidence interval from 1.929 to 4.191, and p < 0.001. The estimates and intervals are close, so the recalculation is consistent with the broad direction and scale of the sponsor’s comparison. It is not a reproduction of ANCOVA: it uses summary statistics and does not apply the stated baseline adjustment.

The registry record does not identify a discrepancy between the sponsor’s analysis and the recalculation. The sponsor’s reported model remains the more appropriate result to cite as the study analysis, because it is the analysis recorded by the sponsor and uses the stated covariate adjustment. The recalculation serves as a limited check, not an alternative sponsor result or a basis for revising the reported analysis.

15. Multiplicity, Missing Data and Analysis Populations

The registry record reports a primary endpoint and a range of secondary outcomes, but it does not report whether the statistical plan adjusted for multiple comparisons. It also does not report a testing hierarchy, a strategy for controlling family-wise error or false discovery, or whether secondary outcomes were intended to be confirmatory or exploratory. Without those details, the strength of evidence from individual secondary p-values cannot be assessed in the context of all the analyses that may have been conducted.

In general, multiplicity matters when several hypotheses are tested: even when none of the effects is real, some results may appear unusual by chance. Adjustments or prespecified testing sequences can address that issue, but no such approach should be assumed without documentation. The primary comparison is distinguishable from the secondary comparisons because it is explicitly identified as the primary endpoint. The available registry record does not establish how the wider family of outcomes was handled statistically.

Information about missing data is also limited. The primary efficacy population requires a baseline measure and post-baseline efficacy data, and the primary description specifies BMD values at both Baseline and Month 6. This makes the analysis population dependent on data availability. The record does not report how missing endpoint measurements were handled, whether imputation was used, what assumptions guided any such procedure, or whether sensitivity analyses examined alternative missing-data assumptions.

The registry describes an Intent-to-Treat Efficacy population that includes randomized participants who received one dose and had specified efficacy measurements. That definition is not identical to an unrestricted analysis of everyone randomized, because receipt of treatment and available measurements are conditions for inclusion. The record does not provide enough detail to determine the impact of exclusions or missing observations, or to compare the result with a separate analysis of all randomized participants.

These omissions do not invalidate the reported result, but they limit independent assessment of robustness. A complete statistical analysis plan and fuller reporting of analysis populations, missingness, and multiplicity would help readers evaluate how sensitive the conclusions are to these choices.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cataract nuclear (0.8%), hypotension (0.8%), varicose vein ruptured (0.8%), asthenia (0.8%), liver abscess (0.8%).

The safety record reports serious adverse events among 124 participants at risk in the denosumab group and 126 at risk in the placebo group. The number with a serious adverse event was 1 for denosumab and 3 for placebo. For other adverse events, the record gives 8 among 124 at risk for denosumab and 3 among 126 at risk for placebo. These are separate categories as recorded; the counts should not be added together because the record does not establish whether categories overlap.

The listed serious adverse-event terms each have a reported frequency of 0.8%: cataract nuclear, hypotension, varicose vein ruptured, asthenia, liver abscess, and hepatic enzyme increased. The registry record does not map each listed term to a treatment group in this summary, so they should not be assigned to one group by inference. Death counts are not reported in the registry record.

These figures are descriptive counts over the study’s safety reporting period. They do not establish that a treatment caused an event, and differences in counts alone do not give a complete comparative safety assessment. The registry record does not provide event-level timing, exposure-adjusted rates, or detailed adjudication information in the material.

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

The primary finding is a between-group difference in the reported mean percent change in lumbar-spine BMD at Month 6. The sponsor’s ANCOVA estimate is 3.05, with a 95% confidence interval from 1.91 to 4.19 and p < 0.001. The unadjusted recalculation is similar in estimate and interval. This supports a statistical distinction between groups for the specified BMD measure under the sponsor’s analysis.

That result does not, by itself, show how the difference translates into outcomes that were not the primary endpoint. The primary measure is BMD, not fractures, pain, mobility, or quality of life. The registry record does not report a threshold for clinical importance, so statistical evidence of a difference should not be equated automatically with a clinically meaningful benefit.

The result also does not answer every question about safety. The record lists serious and other adverse-event counts, but the available counts are descriptive and do not establish causation. The study’s 6-month double-blind treatment period is the timeframe relevant to this primary endpoint; the registry record does not provide evidence from longer follow-up in the material.

Interpretation is bounded by the study population and analysis population. The trial concerns Indian postmenopausal women with osteoporosis, and the primary efficacy analysis includes participants meeting the stated treatment and measurement criteria. The results should not be assumed to apply identically to people outside that population or to settings not represented by the trial.

Finally, a confidence interval describes statistical uncertainty within the analysis, not every uncertainty about design, missing data, measurement, or generalizability. Important details about the original sample-size plan, missing-data handling, and multiplicity are not reported in the registry record. The posted result is best understood as evidence about the measured primary endpoint under the reported analysis, with those broader questions remaining open.

18. Why This Trial Matters Statistically

This trial is statistically informative because it uses a randomized, double-blind, placebo-controlled, parallel-group design and reports a continuous primary endpoint with a model-based comparison. The registry identifies an ANCOVA model that includes baseline lumbar-spine BMD, making the adjustment strategy for the primary comparison explicit at a broad level. The sponsor also reports an estimate, confidence interval, and p-value, allowing readers to consider effect size and precision rather than relying on a significance label alone.

The agreement in broad scale between the sponsor’s ANCOVA result and a simple unadjusted recalculation is a useful consistency check. The two analyses are not identical, however, and recognizing that distinction is central to sound interpretation. The sponsor’s analysis addresses the comparison using the stated model; the recalculation is a summary-statistic check and cannot validate every modeling choice.

The study also illustrates why a positive statistical result is not the end of interpretation. The endpoint is lumbar-spine BMD, while the registry lists other outcomes that address different measurements and safety questions. The clinical importance threshold is not reported, and the primary endpoint does not directly measure all outcomes readers may care about. Precision, endpoint relevance, population, and safety context all matter alongside the p-value.

Finally, the record highlights the value of complete statistical reporting. Details about multiplicity, missing-data methods, the original sample-size justification, and the full statistical plan are not reported in the registry record. Those details would help readers judge how robustly the analysis was planned and how much weight to give secondary findings. The reported estimates remain interpretable, but the limits of the record should remain visible.

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 primary efficacy result is based on an analysis population that requires treatment receipt and available efficacy measurements, including BMD at Baseline and Month 6 for the primary endpoint. The registry record does not report how many otherwise eligible participants were excluded because of missing measurements or how missing values were handled. The potential effect of those choices therefore cannot be assessed from the reported information.

The original sample-size justification and design assumptions are not reported in the registry record. The planning illustrations based on the observed effect are not a substitute for that information. The record also does not report whether any interim analyses were planned or conducted, or provide a full statistical analysis plan.

The primary comparison is reported using ANCOVA, but the detailed model specification and diagnostics are not reported in the registry record. The simple unadjusted recalculation is close to the sponsor’s result, but it cannot test the assumptions or reproduce the sponsor’s model from aggregate summaries.

The trial’s primary follow-up endpoint is at Month 6. The registry record does not provide a longer-term primary comparison in the information described. The primary outcome is BMD at the lumbar spine, not a direct clinical outcome such as fracture occurrence. A clinical-importance threshold for the observed difference is also not reported.

The record lists numerous secondary outcomes, but it does not report a multiplicity strategy. Numerical results for all listed secondary outcomes are not present in the available summaries. Safety figures are descriptive, and the record does not provide event-level details or an explicit causal assessment. These limitations constrain broader conclusions beyond the specified primary comparison.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study in Indian Postmenopausal Women With Osteoporosis to Evaluate the Efficacy and Safety of Denosumab — NCT01495000.
• Registry record last updated 2014-02-07; status last verified 2013-12.
• Results first posted 2013-12-25.
• 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

NCT01495000 is a completed, randomized, double-blind, placebo-controlled, parallel-group Phase 3 study sponsored by GlaxoSmithKline. It enrolled 250 Indian postmenopausal women with osteoporosis. Treatment was a single subcutaneous injection of denosumab 60 mg or placebo at the start of the 6-month double-blind period.

The primary outcome was mean percent change from Baseline in lumbar-spine BMD at Month 6, measured by DXA. The sponsor’s ANCOVA analysis reports a mean difference of 3.05, a 95% confidence interval from 1.91 to 4.19, and p < 0.001. A simple unadjusted recalculation gives 3.06, with a 95% confidence interval from 1.929 to 4.191 and p < 0.001.

The registry lists secondary BMD, bone-marker, safety, vital-sign, and laboratory outcomes. Details of the original sample-size rationale, multiplicity procedures, and missing-data handling are not reported in the registry record.