This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for BiRd vs. Rd as Initial Therapy in Multiple Myeloma (NCT02516696), a randomized phase 3 study. The primary outcome is Survival Duration Without Disease Progression.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02516696 |
| Phase | Phase 3 |
| Condition | Multiple Myeloma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Weill Medical College of Cornell University |
| Results posted | Yes |
2. Clinical Question
Population
People with newly diagnosed multiple myeloma who require treatment, as described in the registry summary. The primary-outcome population field is blank, and further eligibility details are not reported in the registry record.
Intervention
BiRD: clarithromycin, lenalidomide, and dexamethasone, administered in 28-day cycles.
Comparator
Rd: lenalidomide and dexamethasone, administered in 28-day cycles.
Primary question
How does the duration of survival without disease progression compare between the assigned BiRD and Rd regimens? Progression was to be determined using the International Myeloma Working Group Criteria; death from any cause was also part of the endpoint.
This is a question about time to progression or death, not simply whether a response occurred. The registry identifies survival duration without disease progression as the primary outcome and specifies a maximum follow-up timeframe of approximately 5 years. Its summary describes the comparison as an investigation of BiRD versus Rd for initial therapy.
The posted arm-specific medians are 661 days for BiRD and 1694 days for Rd. These are descriptive results for the individual arms. The registry record does not report an arm-to-arm hazard ratio, confidence interval for a comparative effect, or p-value. The posted medians therefore do not, by themselves, establish the size or statistical uncertainty of a treatment contrast. The record also does not report enough information to determine how the trial’s termination affected follow-up or the planned comparison.
3. Trial Design
The registry describes a randomized, open-label, parallel-group phase III study. Participants were assigned to BiRD or Rd. Open-label means that treatment assignment was not masked, according to the registry’s design information; the record does not describe any separate masking of outcome assessors.
The BiRD regimen comprised clarithromycin, lenalidomide, and dexamethasone in 28-day cycles. The Rd regimen comprised lenalidomide and dexamethasone in 28-day cycles. Both were described as initial therapy. The study summary identifies the intended population as newly diagnosed people with multiple myeloma who require treatment.
Enrollment is listed as 12. The posted primary-outcome results include 7 participants in the BiRD arm and 5 in the Rd arm. These figures describe the arm-level counts displayed with the outcome; the registry record does not explain the relationship between those counts and any analysis population, nor does it provide a participant flow account.
The study status is terminated. The registry lists a start date of 2016-02 and a primary completion date of 2022-06-22. The primary endpoint timeframe was until disease progression or death from any cause, for a maximum of approximately 5 years. The reason for termination, the date of termination, and whether the study stopped before its intended enrollment or follow-up were not reported in the registry record.
Randomization is intended to support a fair comparison by reducing systematic differences between treatment groups, but it cannot guarantee balance, particularly in a study with limited enrollment. Because the trial was open-label, knowledge of assigned treatment could potentially influence care or assessment; the registry does not describe procedures intended to address such risks. It also does not report the randomization method, allocation concealment, or a detailed protocol for follow-up.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | BiRD Treatment Regimen | Rd Treatment Regimen |
|---|---|---|
| STARTED | 7 | 5 |
| COMPLETED | 7 | 5 |
| NOT COMPLETED | 0 | 0 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | BiRD Treatment Regimen | Rd Treatment Regimen | Total |
|---|---|---|---|---|
| Participants analysed | 7 | 5 | 12 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 7 | 5 | 12 |
| Sex: Female, Male: Female | Participants | 5 | 2 | 7 |
| Sex: Female, Male: Male | Participants | 2 | 3 | 5 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 7 | 4 | 11 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 | 1 | 3 |
| Race (NIH/OMB): White | Participants | 4 | 2 | 6 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 2 | 3 |
| Region of Enrollment: United States | participants | 7 | 5 | 12 |
6. Primary Endpoint
The registry lists the primary outcome as Survival Duration Without Disease Progression, measured over Until disease progression or death from any cause, for a maximum of approximately 5 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | days |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is survival duration without disease progression, expressed as a median in days. The registry defines the event as disease progression or death from any cause and states that progression is determined by the International Myeloma Working Group Criteria. Follow-up was specified to continue until an event or a maximum of approximately 5 years.
Time-to-event endpoints are used when the timing of an event matters and participants may be followed for different lengths of time. In general, these analyses can account for participants whose event has not been observed by the end of their available follow-up, provided the analysis method and censoring information are available. The registry record does not report the method used to estimate the medians, censoring details, or the number of participants with events.
A median is the point at which the estimated distribution of event times reaches its midpoint. It does not describe every participant’s experience, and it is not the same as an average duration. A confidence interval conveys uncertainty around an estimated quantity; a wider interval generally indicates less precision. The registry lists 95% confidence intervals for the arm-specific medians, but only lower limits are displayed: 586 days for BiRD and 821 days for Rd. Upper limits are not reported in the posted results.
The endpoint can describe how long participants remained alive without recorded progression under each assigned regimen. To assess the comparative treatment effect, however, the arm-specific medians need to be accompanied by a suitable comparative analysis. Such an analysis is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary-outcome medians are 661 days in the BiRD arm and 1694 days in the Rd arm. The respective displayed lower confidence limits are 586 days and 821 days. The registry does not display upper confidence limits for either median. These summaries describe the outcome within each arm; they do not quantify the uncertainty in a direct difference or other comparative effect.
The registry record does not report a hazard ratio, a confidence interval for a hazard ratio, or a p-value for the primary comparison. It also does not post analysis entries for the outcome comparison. The result therefore cannot be read as a completed statistical test of BiRD versus Rd. The medians alone do not establish whether any observed contrast is compatible with chance, nor do they show how event timing was distributed across participants.
Precision is important in interpreting the arm-level values. A confidence interval gives a range of values compatible with the data under the method’s assumptions. Here, the posted information includes only lower confidence limits, so the interval’s full span cannot be assessed from the registry results. The small arm-level counts—7 for BiRD and 5 for Rd—also indicate that the displayed summaries come from a limited set of participants. The record does not provide enough information to evaluate the impact of censoring, missing outcome information, or the number of observed events.
Trial status also matters for context. The study is listed as terminated, but the reason for termination and its consequences for the intended enrollment, follow-up, and analysis are not reported in the registry record. The enrollment entry is 12. No explanation is given for whether termination altered the planned statistical approach or the interpretation of the available results.
The appropriate reading is therefore descriptive and cautious: the registry reports different arm-specific median durations, but it does not post the comparative analysis needed to estimate the effect of assignment to one regimen rather than the other. The record cannot establish a treatment advantage, a treatment disadvantage, or the statistical reliability of the observed medians. A missing comparative estimate is not evidence that the regimens are equivalent.
9. Statistical Methods Explained
The primary endpoint is a time-to-event outcome. In general, a time-to-event analysis considers both whether an event occurred and how long it took to occur. In this study, the event was progression or death from any cause, and the registry specified criteria for determining progression. The analysis method itself is not reported in the registry record.
What does a median time mean?
In general, the median event time is the point at which half of the estimated event-time distribution has experienced the event. It is a description of the distribution’s midpoint, not an average and not a statement that every participant experienced an event at that time. The registry reports medians of 661 days for BiRD and 1694 days for Rd. Those are separate arm-level summaries. Without a reported comparative analysis, their numerical separation is not itself an estimate of a treatment effect with known uncertainty.
What does the confidence interval add?
A confidence interval communicates uncertainty in an estimate under the method used to construct it. In general, it reflects both the observed data and assumptions of the statistical procedure; it is not a guarantee that the true value lies within a particular range. The registry identifies 95% confidence intervals for the medians, but reports only a lower limit for each arm: 586 days for BiRD and 821 days for Rd. Since upper limits are absent, the full intervals cannot be read or compared. The method used to calculate these intervals is not reported in the registry record.
Why is a comparative effect needed?
Comparing two randomized groups requires an estimate that directly relates outcomes across the groups, together with uncertainty around that estimate. For time-to-event outcomes, a hazard ratio is one possible comparative measure. In general, it compares event rates over follow-up under a specified model, and its interpretation depends on that model and the behavior of the event rates over time. The registry record does not report a hazard ratio, its confidence interval, or a p-value for this primary comparison. No comparative effect should be inferred by calculating one from the posted medians.
How can censoring affect interpretation?
General explanation: censoring occurs when a participant’s event time is not observed during the available follow-up, for example because follow-up ends before an event is recorded. Time-to-event methods can use the information available up to that point, but interpretation depends on how censoring is handled and on assumptions about the reasons follow-up ends. The registry specifies a maximum timeframe of approximately 5 years but does not report censoring counts, follow-up distributions, or the statistical method used. It is therefore not possible to assess censoring’s impact from the posted results.
What does over-dispersion mean in general?
General explanation: over-dispersion is a feature of count data in which variability exceeds what a simpler statistical model assumes. It can make standard errors too small if the extra variability is ignored. It is not a reported feature of this primary endpoint, which is a time-to-event outcome, and the registry record does not describe a model for which over-dispersion was assessed. This concept should not be used to reinterpret the posted medians.
What do the planning illustrations represent?
Sample-size planning uses assumptions about the effect to detect, the desired power, the significance level, allocation, and an analysis model. General explanation: a planning calculation asks how much information a future study might need under specified assumptions. It is not a measure of the probability that this completed study detected an effect, and it is not observed power. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect framed as a stated fraction of the observed effect. For time-to-event outcomes, the planning description refers to the total number of events. The registry record does not report a detailed original sample-size justification or the trial’s own design calculations. No planning illustration can replace the missing comparative analysis.
The record also does not report the model diagnostics, analysis conventions, or sensitivity analyses used for the primary endpoint. Consequently, the posted arm-specific medians and lower confidence limits should be treated as limited descriptive summaries, not as a full account of the trial’s statistical evidence.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 11 outcome measures and 10 posted secondary outcomes. The listed secondary outcomes include overall response rate, adverse events, overall survival, and measures of response, event-free survival, duration of response, and progression. The record does not report a hierarchy for testing these outcomes, a prespecified strategy for controlling multiplicity, or whether any outcomes were designated as exploratory. When several outcomes are examined, general statistical practice recognizes that the chance of at least one apparently unusual result can increase unless the analysis plan addresses multiple testing. Whether or how that issue was handled in this trial is not reported in the registry record.
No registry analysis entries are posted for the primary outcome comparison. The record does not report an intention-to-treat analysis, a per-protocol analysis, or another defined analysis population. Although arm-level outcome counts are listed, their relationship to the analyzed population is not explained. The primary-outcome population field is blank.
Missing-data handling is also not reported in the registry record. There is no description of how absent assessments, loss to follow-up, withdrawals, or incomplete outcome information were treated. For time-to-event outcomes, censoring can be distinct from missing data, but the record does not provide the information needed to understand either process in this study. The registry does not explain the number or timing of censored observations.
These omissions limit assessment of whether the posted summaries correspond to the originally planned analysis and how robust they are to alternative assumptions. They do not establish that data were missing or that analyses were improperly conducted; they mean that the relevant details are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| BiRD Treatment Regimen | 6 | 7 | 85.7% |
| Rd Treatment Regimen | 3 | 5 | 60.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| BiRD Treatment Regimen | 2 of 7 |
| Rd Treatment Regimen | 4 of 5 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| BiRD Treatment Regimen | 7 of 7 |
| Rd Treatment Regimen | 5 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | BiRD Treatment Regimen | Rd Treatment Regimen |
|---|---|---|---|
| Fall | General disorders | 2 of 7 | 1 of 5 |
| Syncope | General disorders | 2 of 7 | 0 of 5 |
| Cellulitis | Skin and subcutaneous tissue disorders | 1 of 7 | 0 of 5 |
| Allergic Reaction | General disorders | 1 of 7 | 0 of 5 |
| Urinary Tract Infection | Renal and urinary disorders | 1 of 7 | 0 of 5 |
| Acute Hypoxic Respiratory Failure | Respiratory, thoracic and mediastinal disorders | 1 of 7 | 0 of 5 |
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | 1 of 7 | 0 of 5 |
| Constipation | Gastrointestinal disorders | 0 of 7 | 1 of 5 |
| Secondary Primary Malignancy | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 7 | 1 of 5 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 0 of 7 | 1 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | BiRD Treatment Regimen | Rd Treatment Regimen |
|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | 3 of 7 | 2 of 5 |
| Fatigue | General disorders | 3 of 7 | 2 of 5 |
| Constipation | Gastrointestinal disorders | 3 of 7 | 1 of 5 |
| Edema Limbs | General disorders | 2 of 7 | 2 of 5 |
| Pain | General disorders | 2 of 7 | 2 of 5 |
| Maculo-papular rash | Skin and subcutaneous tissue disorders | 2 of 7 | 2 of 5 |
| Anorexia | General disorders | 1 of 7 | 2 of 5 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 1 of 7 | 2 of 5 |
| Dyspepsia | Gastrointestinal disorders | 1 of 7 | 2 of 5 |
| Hypocalcemia | Investigations | 2 of 7 | 1 of 5 |
Serious events with the highest arm-level rate: fall (28.6%), syncope (28.6%), constipation (20.0%), secondary primary malignancy (20.0%), dyspnea (20.0%).
The registry lists serious adverse event information by arm. For BiRD, the serious-event group lists 7 at risk and 6 affected; for Rd, it lists 5 at risk and 3 affected. These are registry counts and should not be treated as a complete description of event types, timing, severity, or causal attribution. The record also lists other adverse events: 7 at risk and 7 affected in BiRD, and 5 at risk and 5 affected in Rd.
Deaths are listed as 2 for BiRD and 4 for Rd. The registry information does not establish whether these deaths were related to treatment, when they occurred, or how they relate to the primary endpoint. Death from any cause is part of the primary progression-free survival endpoint, but the safety figures alone do not supply an arm-to-arm safety comparison.
Serious-event terms listed in the registry include Fall and Syncope, each at 28.6%, and Constipation, Secondary Primary Malignancy, Dyspnea, and Acute Kidney Injury, each at 20.0%. The record does not specify in the listed term information the denominator or arm attribution for these percentages. They should therefore be read as reported term frequencies, not as comparative risks between regimens. With the limited arm-level counts, the safety summaries are descriptive and do not establish whether one regimen has a different safety profile.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, open-label phase III study was conducted to compare BiRD with Rd as initial therapy for newly diagnosed multiple myeloma requiring treatment. It reports arm-specific median progression-free survival durations and lower confidence limits, along with limited adverse-event counts. Those are the posted outcome summaries that can be described directly.
The record does not establish a comparative treatment effect. No primary-outcome hazard ratio, comparative confidence interval, or p-value is reported. Separate medians are not a substitute for such an analysis, and their difference should not be calculated or interpreted as a direct treatment effect. The reported values do not show whether the observed contrast is statistically reliable or how precisely a comparative effect was estimated.
The results also do not establish that the treatments are equivalent. Failure to report a comparative test is not evidence of no difference. Nor does the record establish the reason for the medians or whether they reflect differences in treatment, participant characteristics, follow-up, or chance. Randomization supports comparison in principle, but the limited enrollment and missing analysis details constrain what can be concluded from the registry results.
The safety counts are similarly descriptive. The record does not report causal attribution, timing, or an adequately specified comparison of adverse-event risk. The listed term percentages lack an explicitly stated denominator and arm attribution in the available information. They should not be used to make a comparative safety claim.
In short, the registry documents the trial’s design and posts some arm-level summaries, but it does not provide a complete statistical account of the primary comparison. The findings should be understood as reported descriptive information rather than proof that either regimen is superior, inferior, or equivalent.
13. Why This Trial Matters Statistically
This trial illustrates why a randomized design and a reported comparative analysis are both important. Random assignment is intended to support comparisons between treatment groups, while the analysis quantifies the difference and its uncertainty. The registry reports arm-specific medians but no comparative estimate for the primary outcome. That distinction helps prevent readers from treating separate group summaries as though they were a formal test of the treatment contrast.
The record also highlights the role of precision. Confidence intervals are reported for the medians, but only their lower limits are displayed. Without complete intervals or a comparative interval, readers cannot assess the full uncertainty around the reported values. This is particularly relevant when the arm-level counts are limited, as they are in this registry entry.
The terminated status adds an important reporting question. The reason for termination and its consequences for enrollment, follow-up, and analysis are not reported in the registry record. These details matter when assessing whether the results represent the originally intended study and how much information the available data contain.
Finally, the trial includes multiple outcome measures, while the registry does not describe a testing hierarchy or multiplicity strategy. Transparent reporting of the analysis plan, analysis populations, missing-data handling, and outcome-specific results would help readers assess how the evidence was generated. The posted record can still be read accurately: it documents the intended randomized comparison and describes some outcomes, while leaving the central comparative statistical evidence unavailable.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry lists enrollment as 12, with outcome counts of 7 for BiRD and 5 for Rd. The arm-level results therefore come from a limited set of participants, and the record does not report event counts for the primary endpoint. The reason for the trial’s terminated status and its effect on the available data are not reported in the registry record.
For the primary endpoint, only arm-specific medians and lower confidence limits are posted. Upper confidence limits, a hazard ratio, a comparative confidence interval, and a p-value are not reported. The registry does not describe the method used to estimate the medians, the treatment of censoring, or the analysis population. These gaps prevent assessment of the precision and robustness of the primary comparison.
The record does not report participant characteristics, a flow of participants through the study, adherence to assigned treatment, or details of follow-up. It also does not describe the randomization procedure, allocation concealment, or any procedures for handling the open-label design. These items are not evidence of a particular problem; they are information not reported in the registry record.
Safety summaries lack details about event timing and treatment attribution. The listed serious-event term percentages do not specify an arm or denominator in the available information, which limits interpretation. The record also does not report a multiplicity strategy, missing-data procedures, or the definitions of analysis populations. Together, these limitations mean that the registry supports a description of the posted outcomes but not a comprehensive appraisal of the treatment comparison.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: BiRd vs. Rd as Initial Therapy in Multiple Myeloma — NCT02516696.
- Registry record last updated 2023-06-05; status last verified 2023-06.
- Results first posted 2023-06-05.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT02516696 is listed as a randomized, open-label, parallel-group phase III study of BiRD versus Rd as initial therapy for multiple myeloma. BiRD comprised clarithromycin, lenalidomide, and dexamethasone in 28-day cycles; Rd comprised lenalidomide and dexamethasone in 28-day cycles. The registry describes the intended population as newly diagnosed people requiring treatment.
The primary outcome was survival duration without progression, with death from any cause also counted and progression determined by International Myeloma Working Group Criteria. The registry reports median durations of 661 days for BiRD and 1694 days for Rd, with lower confidence limits of 586 days and 821 days, respectively; upper limits are not posted. No comparative primary-outcome analysis is reported in the registry record.
Enrollment is listed as 12, and study status is terminated. The reason for termination, analysis populations, missing-data handling, and a comparative estimate are not reported in the registry record. The available results are descriptive and do not establish a treatment advantage or equivalence.