Phase 2 Study of BA058 (Abaloparatide) Transdermal Delivery in Postmenopausal Women With Osteoporosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2 Study of BA058 (Abaloparatide) Transdermal Delivery in Postmenopausal Women With Osteoporosis (NCT01674621), a randomized phase 2 study. The primary outcome is Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at 6 Months.

2. Clinical Question

The registry describes a study of clinical safety and efficacy, with BMD and serum markers of bone metabolism among its outcomes. The primary endpoint was specifically the percent change in lumbar-spine BMD from baseline to 6 months. The listed comparisons also include an active injection group, which allows the registry to show outcome summaries for that treatment group alongside those for the transdermal groups and placebo.

This question is about the endpoint and comparisons recorded for the trial, not whether a treatment should be used. The registry record does not report a prespecified threshold for a clinically important BMD change. It also does not report a treatment-effect interpretation that would establish how the measured changes relate to later clinical outcomes.

3. Trial Design

This was a randomized, double-blind, placebo-controlled, phase 2 study with a parallel-group design and triple masking recorded. The sponsor was Radius Health, Inc. The registry enrollment was 250. The study started on 2012-09-25, had primary completion on 2013-08-02, and is listed as completed.

The interventions were three daily transdermal microarray patch doses of abaloparatide, an 80 mcg daily subcutaneous abaloparatide injection, and a transdermal placebo patch. Each intervention description specifies treatment for up to 6 months. The active injection serves as a comparator arm in the trial, while the transdermal placebo provides the placebo comparison for the patch groups.

The primary endpoint population was not simply defined as everyone enrolled. It was the mITT population, including participants with pretreatment and end-of-treatment evaluable radiologic assessments, analyzed according to randomized assignment. The primary endpoint summaries list 47 participants in the 50 mcg group, 46 in the 100 mcg group, 43 in the 150 mcg group, 49 in the injection group, and 46 in the placebo group. These are endpoint-specific analysis counts and should not be read as the number enrolled in the study.

The registry describes the trial as enrolling otherwise healthy postmenopausal women with osteoporosis. The duration specified for treatment and the primary endpoint was 6 months. Details such as the method used to generate the randomization sequence, the parties included in triple masking, and the original sample-size justification are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: mITT population included all participants with pretreatment and end-of-treatment evaluable radiologic assessments. The participants were analyzed as randomized.

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.

Population: Modified Intent-to-Treat (mITT) population included randomized participants with pretreatment and end-of-treatment evaluable radiologic assessments.

6. Primary Endpoint

The registry lists the primary outcome as Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at 6 Months, measured over Baseline, 6 Months.

The primary endpoint was percent change from baseline in lumbar-spine BMD at 6 months, measured with dual energy x-ray absorptiometry (DXA). BMD is a continuous measurement of bone mineral content in a specified skeletal region. A percent change expresses the end-of-treatment measurement relative to the baseline measurement, rather than reporting only a final value.

The lumbar spine was the prespecified primary measurement location in the registry. This makes the endpoint the main outcome used to assess the trial's central question, while measurements at other locations and serum bone-metabolism markers are secondary outcomes. The registry record does not give a clinical-importance threshold for interpreting a particular percentage change.

For each arm, the posted result is a mean percent change with a standard deviation. The mean describes the group's average observed change; the standard deviation describes how dispersed individual measurements were around that average. The result therefore conveys both the central pattern and the variability in the analyzed group, but the mean alone does not describe every participant's outcome.

The endpoint population required evaluable radiologic assessments before treatment and at the end of treatment. Consequently, its summaries describe participants meeting that criterion, analyzed as randomized, rather than necessarily every enrolled participant. The record does not report further detail about how missing endpoint measurements were handled beyond this population definition.

7. Results Posted in the Registry

• Abaloparatide Transdermal (50 mcg): mean 1.87 versus 0.04 on control; difference 1.83 (95% CI 0.74 to 2.92), standardized effect d = 0.68; z-test p = <0.001.
• Abaloparatide Transdermal (100 mcg): mean 2.33 versus 0.04 on control; difference 2.29 (95% CI 1.18 to 3.40), standardized effect d = 0.84; z-test p = <0.001.
• Abaloparatide Transdermal (150 mcg): mean 2.95 versus 0.04 on control; difference 2.91 (95% CI 1.73 to 4.09), standardized effect d = 1.04; z-test p = <0.001.
• Abaloparatide Injection (80 mcg): mean 5.80 versus 0.04 on control; difference 5.76 (95% CI 4.38 to 7.14), standardized effect d = 1.66; 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.

Percent Change From Baseline in BMD of Total Hip at 6 Months

• 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:
  • Abaloparatide Transdermal (50 mcg): mean 0.97 versus -0.02 on control; difference 0.99 (95% CI 0.10 to 1.88), standardized effect d = 0.45; z-test p = 0.029.
  • Abaloparatide Transdermal (100 mcg): mean 1.32 versus -0.02 on control; difference 1.34 (95% CI 0.45 to 2.23), standardized effect d = 0.61; z-test p = 0.003.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Abaloparatide Transdermal (50 mcg) 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 mean is statistically higher for Abaloparatide Transdermal (100 mcg) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percent Change From Baseline in BMD of Forearm at 6 Months

• 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:
  • Abaloparatide Transdermal (50 mcg): mean -0.24 versus 0.05 on control; difference -0.29 (95% CI -1.50 to 0.92), standardized effect d = -0.10; z-test p = 0.638.
  • Abaloparatide Transdermal (100 mcg): mean -0.16 versus 0.05 on control; difference -0.21 (95% CI -1.62 to 1.20), standardized effect d = -0.06; z-test p = 0.771.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Abaloparatide Transdermal (50 mcg) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Abaloparatide Transdermal (100 mcg) and the control. The interval gives the range of effects that remain compatible with the data.

Percent Change From Baseline in Serum Bone-Specific Alkaline Phosphatase (BSAP) at 6 Months

• 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:
  • Abaloparatide Transdermal (50 mcg): mean -4.84 versus 10.23 on control; difference -15.07 (95% CI -35.04 to 4.90), standardized effect d = -0.31; z-test p = 0.139.
  • Abaloparatide Transdermal (100 mcg): mean 5.22 versus 10.23 on control; difference -5.01 (95% CI -27.62 to 17.60), standardized effect d = -0.09; z-test p = 0.664.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Abaloparatide Transdermal (50 mcg) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Abaloparatide Transdermal (100 mcg) and the control. The interval gives the range of effects that remain compatible with the data.

The registry identifies secondary outcomes covering BMD at the total hip and forearm, serum markers of bone metabolism, and abnormal physical examinations. The numerical summaries available in the registry record for the secondary outcomes show a less uniform pattern than the primary lumbar-spine result. Total-hip BMD means are positive in the active groups and close to zero in placebo, while forearm BMD changes are mixed and close to zero across the reported groups. The BSAP results are variable, with substantial spread around group means. These different patterns are not unexpected: outcomes at different skeletal sites and biochemical measures capture different aspects of bone biology.

The sponsor reports Dunnett p-values for selected transdermal-versus-placebo secondary comparisons. Separately, the unadjusted recalculations include estimates for selected total-hip contrasts. These analyses do not cover every secondary comparison, and their statistical status differs. The results should be viewed as supportive or exploratory context for the primary lumbar-spine endpoint, not as independent confirmation of it.

Secondary endpoints involve multiple outcomes and, in some cases, multiple treatment comparisons. Without a clearly reported multiplicity plan for the full set, unadjusted findings carry less weight because the chance of at least one apparently notable result increases as more comparisons are examined. The statistical plan for the secondary outcomes is not reported in the registry record. Numerical results for PICP, osteocalcin, PINP, CTXI, and abnormal physical examinations are not reported in the registry record.

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

• Percent Change From Baseline in BMD of Total Hip at 6 Months
• Percent Change From Baseline in BMD of Forearm at 6 Months
• Percent Change From Baseline in Serum Bone-Specific Alkaline Phosphatase (BSAP) at 6 Months
• Percent Change From Baseline in Serum Procollagen Type I C Propeptide (PICP) at 6 Months
• Percent Change From Baseline in Serum Osteocalcin at 6 Months
• Percent Change From Baseline in Serum Procollagen Type I N Propeptide (PINP) at 6 Months
• Percent Change From Baseline in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (CTXI) at 6 Months
• Number of Participants With Abnormal Physical Examinations at Screening and End of Treatment (6 Months)

9. Statistical Interpretation

10. Statistical Methods Explained

For a continuous outcome such as percent change in BMD, a group mean summarizes the average observed value, while the standard deviation describes variability among individual values. A mean difference compares two group averages. In the posted recalculations, each active arm is compared with transdermal placebo. The estimate is expressed in the endpoint's units, percentage points of change, and remains an unadjusted comparison based on posted summary statistics.

What does a confidence interval convey?

A confidence interval describes the uncertainty around an estimated contrast under the statistical method used to construct it. A narrower interval indicates greater precision, while a wider interval indicates that the estimate is less precise. An interval that includes zero is compatible with no difference under that method; an interval that excludes zero is evidence against a zero difference at the corresponding confidence level. This general interpretation does not say whether a difference is clinically important.

The registry's recalculated contrasts include intervals for each active group versus placebo. For the primary endpoint, each recalculated interval excludes zero. The registry does not label the confidence level for these recalculated intervals in the listed comparison details, so it should not be assumed from those details alone. The sponsor's separate patch-versus-injection results explicitly identify their intervals as 95% confidence intervals.

Why distinguish the sponsor analysis from recalculation?

The registry includes sponsor-reported analyses as well as recalculations made from the posted group summaries. The sponsor used Dunnett's test for the patch-dose comparisons against the shared placebo group. That procedure accounts for the family of comparisons with a common control. The recalculated mean differences and intervals are simple, unadjusted comparisons and do not reproduce that multiplicity adjustment. They can help readers understand the magnitude and precision of the group contrasts, but the sponsor's own analysis is the relevant registered analysis for those comparisons.

The sponsor also reported contrasts between patch groups and injection for final values. Those estimates are explicitly described as mean differences in final values, whereas the recalculations presented for the primary endpoint compare change from baseline with placebo. Differences in comparison group and outcome definition mean that the estimates should not be treated as interchangeable.

Why can variability affect precision?

Standard deviation measures how spread out observations are within a group. When individual results vary substantially, the group mean is generally less precisely estimated than it would be with the same number of observations and less variability. The standard deviations for the BMD endpoint provide context for the mean results, but they do not show the full distribution, identify unusual observations, or reveal whether the assumptions of a particular analysis were satisfied.

General statistical explanation: over-dispersion means that variation in the observed data is greater than a model assumes. If a model understates variability, standard errors can be too small and intervals can be too narrow. This concern is especially relevant when a model's variance assumptions do not fit the outcome. The primary endpoint is continuous, and the registry record does not report an over-dispersion assessment or a model-based adjustment for it.

What role does the analysis population play?

The primary analysis is described as mITT. It includes participants with pretreatment and end-of-treatment evaluable radiologic assessments and analyzes them as randomized. Analyzing as randomized preserves the assigned groups in the analysis, but requiring endpoint assessments means the population is conditional on evaluability. The registry record does not report the number or characteristics of participants without evaluable endpoint measurements, nor does it describe an imputation method or sensitivity analysis for missing BMD values.

The study is listed as randomized, parallel, double-blind, placebo-controlled, and triple-masked. These design features describe the structure of the trial, but details of the randomization method and exactly which groups of people were masked are not reported in the registry record. The statistical analysis plan, including any interim analyses or other model specifications, is not reported in the registry record.

11. Confidence Intervals and Precision

Precision is about how tightly the data locate an estimated treatment contrast. The recalculated primary endpoint estimates are positive for each comparison with placebo, and their intervals exclude zero. That is consistent with the small unadjusted p-values, but an interval and a p-value answer related rather than identical questions: the interval gives a range of estimates compatible with the method, while the p-value measures how inconsistent the data are with a specified null value.

The recalculated mean differences were 1.83 for the 50 mcg patch, 2.29 for the 100 mcg patch, 2.91 for the 150 mcg patch, and 5.76 for injection. The interval for the first patch comparison extends from 0.743 to 2.918; the intervals for the other patch doses extend from 1.176 to 3.404 and from 1.733 to 4.087. The injection comparison interval extends from 4.382 to 7.138. These interval widths show that the estimates retain uncertainty, even where the intervals exclude zero.

These are unadjusted recalculated intervals from the posted summary statistics. They do not reflect the sponsor's Dunnett adjustment for the patch-versus-placebo family of comparisons. The sponsor reports adjusted test results, but the registry record does not provide sponsor confidence intervals for those patch-versus-placebo contrasts. For patch-versus-injection comparisons, the sponsor does report 95% intervals for differences in final values; those contrasts address a different comparison and outcome summary.

Precision should not be confused with clinical importance. A result may be estimated relatively precisely without establishing whether its magnitude matters to patients. The registry record does not state a threshold for a clinically meaningful BMD change or provide a link between the measured endpoint and later clinical outcomes.

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 planning figures are participants per arm for comparisons between two groups. They are not totals across arms and are not total event counts: the outcome is continuous, not time-to-event. Each scenario scales the planning target to a stated fraction of the observed effect. For example, the rows labeled as planning for 75% of the observed effect assume a smaller difference than the row based on the full observed effect.

The calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. Under those assumptions, the 80% power column gives the estimated participants per arm for a design with an 80% probability of detecting the assumed effect if that effect is the true one. The 90% power column gives the corresponding planning count for a 90% probability. These are design probabilities under the calculation's assumptions, not probabilities that the trial result is true.

Smaller effects require more participants to detect with the same target power, because they are harder to distinguish from random variation. The planning figures are illustrations based on the observed effect, not the trial's original design calculation. The trial's own sample-size assumptions are not reported in the registry record. This is not observed power: observed power is not a useful substitute for interpreting the estimate, its confidence interval, and the design of the analysis after results are known.

These calculations also do not automatically account for all features of the trial, including multiple comparisons, missing endpoint measurements, or any analysis details not reported in the registry record. They should therefore be read as conditional planning illustrations, not as a reconstruction of the study's actual enrollment decision.

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 = 1.830; pooled standard deviation σ = 2.680.
2. n = 2 × (1.96 + 0.842)² × 2.680² / 1.830² = 33.7, rounded up to 34 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 <- 1.83                      # observed difference in means
sigma <- 2.67967092452343                     # 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(1674621)
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 = 34 (80% power), 46 (90% power)
 75% of observed effect: n per arm = 60 (80% power), 81 (90% power)
 50% of observed effect: n per arm = 135 (80% power), 181 (90% power)
power.t.test: 34.6 
Simulated power at n = 34 per arm: 0.795 (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's reported primary comparisons are the patch doses against the transdermal placebo group using Dunnett's test. The reported p-values are 0.007 for 50 mcg, 0.001 for 100 mcg, and < 0.001 for 150 mcg. Dunnett's test is appropriate to a set of treatment-versus-common-control comparisons and accounts for their multiplicity in a way that separate unadjusted tests do not.

The recalculated estimates compare changes from baseline with placebo using the posted means and standard deviations. They give mean differences of 1.83, 2.29, and 2.91 for the patch doses, with unadjusted p-values of <0.001 for each. The broad conclusion that the patch groups' mean changes differ from placebo is consistent across the reported and recalculated analyses. The numerical p-values need not match because the recalculations are unadjusted and use summary-statistic methods rather than the sponsor's reported Dunnett analysis.

The sponsor also reports patch-versus-injection mean differences in final values, with 95% confidence intervals. Those comparisons are not the same as the recalculated change-from-baseline contrasts against placebo. They should be interpreted according to their stated estimand and comparator, rather than used as a direct check of the recalculated placebo comparisons.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several statistical hypotheses are tested. Even when each individual test uses a conventional significance threshold, testing a collection of hypotheses increases the chance of at least one result appearing statistically notable by chance. This matters in a trial with several doses, a placebo comparison, an injection group, and multiple secondary outcomes.

For the primary patch-versus-placebo comparisons, the sponsor reports using Dunnett's test. This method is designed for several treatment groups compared with one common control and addresses multiplicity within that family. The recalculated comparisons are explicitly unadjusted, so their p-values should not be read as multiplicity-adjusted evidence. The registry record does not report a comprehensive plan describing how multiplicity was managed across all primary and secondary outcomes, nor does it describe a hierarchy or gatekeeping procedure.

The primary endpoint population is described as mITT: participants had to have evaluable radiologic assessments before treatment and at the end of treatment, and were analyzed as randomized. This definition makes the endpoint results dependent on having those assessments. The registry record does not report how many participants lacked evaluable results, reasons for missing assessments, or whether missing data were imputed. It also does not report sensitivity analyses assessing the effect of missing data.

The record gives endpoint analysis counts for each group, but these do not by themselves explain why the analysis counts differ from the registry enrollment or whether all participants assigned to a group contributed to every endpoint. The randomization method, detailed analysis plan, and interim-analysis procedures are not reported in the registry record. These omissions limit assessment of the full inferential framework and of how robust the findings are to analysis 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: colitis (2.1%), osteoarthritis (2.1%), malignant melanoma (2.0%), coronary artery disease (2.0%), abdominal pain (2.0%).

The registry lists serious adverse event counts by group alongside the number at risk for that safety summary. The counts of participants affected were 0 of 50 in the 50 mcg transdermal group, 2 of 51 in the 100 mcg group, 2 of 47 in the 150 mcg group, 4 of 51 in the injection group, and 1 of 50 in the transdermal placebo group. These are group-specific counts; they should not be added together to infer a total number of distinct participants.

The record also lists serious-event terms, including colitis, osteoarthritis, malignant melanoma, coronary artery disease, abdominal pain, and radius fracture. The recorded terms and percentages describe events listed in the registry; they do not establish that treatment caused an event. The death counts are not reported in the registry record.

Safety counts provide descriptive information, not a precise comparison of risks. The study is a phase 2 trial with follow-up specified for up to 6 months, and the registry record does not provide an inferential analysis of serious adverse events. Absence of a listed serious event in a group does not establish absence of risk.

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

The primary endpoint results show positive mean lumbar-spine BMD percent changes in all three transdermal abaloparatide groups and in the injection group, while the placebo group's mean was close to zero. The recalculated mean differences versus placebo are positive, and their unadjusted intervals exclude zero. The sponsor's Dunnett analyses also report statistical evidence for the patch-dose comparisons against placebo. These statements describe the posted data and analyses for this endpoint.

They do not establish that every participant experienced an increase, because group means can conceal variation and different individual responses. They do not establish that the observed changes are clinically important: the registry record does not give a threshold for meaningful change. Nor do these BMD results establish effects on fractures, long-term outcomes, or outcomes beyond the reported treatment period.

The injection group had the largest posted mean change, but the available comparisons do not provide a full, multiplicity-adjusted set of direct tests among all active treatments. The sponsor's reported patch-versus-injection results use final values, whereas the recalculated primary comparisons use change from baseline against placebo. Those results should not be treated as interchangeable evidence of comparative effectiveness.

Interpretation also depends on the analysis population, which required evaluable radiologic assessments at baseline and end of treatment. The registry does not describe missing-data sensitivity analyses. Secondary findings span different measures and do not have a fully reported multiplicity plan. The safest reading is therefore confined to the endpoint, population, time point, and analyses actually reported.

18. Why This Trial Matters Statistically

This trial illustrates why an average treatment contrast, its uncertainty, and the analysis method all matter. The primary endpoint is continuous, so the posted means and standard deviations reveal both the direction of group averages and variation within groups. The recalculated differences quantify the contrast with placebo, while intervals convey uncertainty around those estimates.

It also demonstrates the distinction between an unadjusted reanalysis and the sponsor's reported analysis. Multiple doses share a placebo comparator, and Dunnett's test addresses that comparison structure. Unadjusted p-values can be useful for understanding simple contrasts, but they should not replace the sponsor's analysis or be interpreted as if they account for a family of tests.

The study has several active arms, multiple secondary measures, and an endpoint-specific analysis population. Those features make multiplicity, missing measurements, and precise definitions of the estimand important. The registry reports some of these details, but not a complete statistical analysis plan or the handling of missing endpoint data. This limits how fully readers can evaluate the robustness of the findings.

Finally, the sample-size illustrations are based on observed effects and explicit planning assumptions; they are not evidence that the original trial was designed around those assumptions. Distinguishing design planning from observed results helps prevent retrospective power calculations from being mistaken for evidence about the certainty or importance of the findings.

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 does not report the trial's original sample-size justification or detailed statistical analysis plan. It also does not specify the randomization procedure, the parties included in triple masking, or whether interim analyses were conducted. These missing details limit assessment of the prespecified analysis choices.

The primary endpoint analysis required evaluable radiologic assessments before treatment and at the end of treatment. The record does not describe the amount, reasons, or pattern of missing endpoint data, or report imputation and sensitivity analyses. The endpoint summaries therefore cannot show whether missing measurements could have influenced the estimates.

Although Dunnett's test is reported for the primary patch comparisons with placebo, a complete multiplicity strategy across the trial's outcomes and comparisons is not reported. The additional recalculations are unadjusted. Secondary numerical results are not reported for several listed outcomes, including serum PICP, osteocalcin, PINP, CTXI, and abnormal physical examinations.

The primary results address a 6-month BMD measure in the specified mITT population. The registry record does not report a clinical-importance threshold for the endpoint, or results establishing effects on fracture outcomes or longer-term outcomes. The safety summary is descriptive, and the registry does not report a comparative inferential analysis of adverse events. These limitations constrain conclusions to the recorded outcomes and follow-up.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Phase 2 Study of BA058 (Abaloparatide) Transdermal Delivery in Postmenopausal Women With Osteoporosis — NCT01674621.
• Registry record last updated 2020-06-16; status last verified 2020-05.
• Results first posted 2016-12-19.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

NCT01674621 is a completed randomized, double-blind, placebo-controlled phase 2 parallel-group trial sponsored by Radius Health, Inc. It enrolled postmenopausal women with osteoporosis and compared three daily abaloparatide transdermal patch doses with transdermal placebo and daily abaloparatide injection over up to 6 months.

The primary outcome was percent change from baseline in lumbar-spine BMD at 6 months. The posted group means were positive in each active-treatment arm and close to zero with placebo. Sponsor-reported Dunnett tests found statistical differences for the patch-dose comparisons against placebo; unadjusted recalculations likewise produced positive mean differences with intervals excluding zero. Interpretation is limited by unreported details about the original statistical plan, missing-data handling, and the clinical importance of the measured changes.