Cross Over Convenience And Preference Study Of New Mark VII Compared To Genotropin Pen In Pediatric And Adult Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cross Over Convenience And Preference Study Of New Mark VII Compared To Genotropin Pen In Pediatric And Adult Subjects (NCT01112865), a randomized phase 3 study. The primary outcome is Percentage of Dyads (Participant and Caregiver or Parent) and Adult Participants Reporting no Difference or Easier to Use for the New Genotropin Mark VII Injection Pen Compared to the Genotropin Pen®.

2. Clinical Question

3. Trial Design

This was a multicenter, randomized, open-label, two-arm crossover study, listed as Phase 3. The registry record lists enrollment of 120 participants and a completed status. Its stated focus was dyad and adult participant perceptions of convenience and preference for the newly developed Mark VII pen compared with the Genotropin pen.

Randomization assigned participants to one of two sequences. One sequence used the Mark VII pen for 2 months and then the current pen for 2 months. The other sequence reversed that order. In a crossover design, participants experience both interventions, and their responses can reflect perceptions formed during each period. The sequence is therefore part of the design, not merely a way of labeling separate treatment groups.

The study was open-label, so participants and caregivers were not masked to which pen they were using. That matters because the main outcome was a reported perception of ease of use and preference. Knowledge of the device could affect expectations or questionnaire responses; the registry record does not describe measures intended to address that possibility. It also does not report whether other people involved in assessing or analyzing outcomes were masked.

The primary outcome was assessed at Month 4 with a question from Section II of the Injection Pen Assessment Questionnaire. Participants compared both pens and chose which was easier overall, with choices of Genotropin Pen® easier, the new injection pen easier, or no difference. The record also lists secondary outcomes concerning preference, ease of use, pen choice, and ease ratings for each pen.

The study began in 2010-08, had primary completion in 2011-10, and is recorded as completed. Further details of the protocol, such as sequence generation, allocation concealment, period-specific analysis, or adjustment for potential carryover effects, 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.

First Intervention

Second Intervention

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS): randomized participants who used a study pen at least once to administer somatropin; Number of participants analyzed (N)= participants with evaluable data. Dyad defined as the participant (child being treated) and adult partner (parent or caregiver).

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 Percentage of Dyads (Participant and Caregiver or Parent) and Adult Participants Reporting no Difference or Easier to Use for the New Genotropin Mark VII Injection Pen Compared to the Genotropin Pen®, measured over Month 4.

The primary endpoint is a percentage based on participants’ answers to a comparative usability question at Month 4. The question asked respondents to think about the Genotropin pen and the new injection pen used over the past few months and choose which was easier overall. The available answers were that the Genotropin pen was easier, that the new pen was easier, or that there was no difference.

The registry’s endpoint title groups reports of “no difference” or “easier to use” for the new Mark VII pen. This makes the outcome a combined response category: it treats a report of equal ease and a report favoring the new pen as meeting the stated endpoint. It does not, by itself, distinguish how many respondents selected each of those answers. The record does not provide the percentage, confidence interval, or category-level counts.

A questionnaire outcome is relevant to a study about convenience and preference because it records participants’ perceptions rather than an objective device-performance measure. In this study, dyads and adult participants were the respondents of interest. The stated analysis population included randomized participants who used a study pen at least once to administer somatropin, with the number analyzed determined by evaluable data.

The percentage can describe how common the specified response was among those analyzed, but its interpretation depends on who answered and how missing or unevaluable questionnaires were handled. Those details and the actual endpoint result are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

A randomized crossover study assigns participants to sequences of interventions and has participants experience each intervention over separate periods. Here, one sequence began with the Mark VII pen and then switched to the current Genotropin pen; the other used the reverse order. This differs from a parallel-group trial, where participants generally remain in one assigned group. A crossover can make each participant’s experience with one intervention informative in relation to that same participant’s experience with the other.

What randomization contributes

Random allocation helps prevent deliberate or systematic assignment of particular participants to a particular sequence. It does not ensure that the realized groups are identical in every respect, and it does not remove all possible sources of bias. The registry record states that allocation was randomized, but details of the randomization procedure and allocation concealment are not reported. Allocation concealment concerns whether assignment could be anticipated before a participant entered the study; it is distinct from masking after assignment.

What an open-label design means

In an open-label study, participants know which intervention they are using. That can be especially relevant when the outcome is a personal assessment of convenience or ease rather than a measurement made independently of the participant’s perceptions. Awareness does not make a reported preference meaningless, but it means the outcome reflects experience in an unmasked setting. The registry record says masking was none. It does not describe whether assessors or analysts were masked, or whether expectations were measured.

Understanding the percentage endpoint

A percentage expresses the number of participants meeting a defined response category in relation to the number evaluated. For this endpoint, the category named in the registry combines “no difference” with “new injection pen easier to use.” The denominator is described as participants with evaluable data. A percentage is therefore meaningful only alongside a clear denominator and response definition. The record does not report the actual denominator or the observed percentage.

The endpoint uses a participant-reported outcome questionnaire. Such measures can capture experiences that are directly relevant to convenience, but their interpretation depends on the wording, response choices, and timing of the question. Here, the question asks for an overall comparison after use of both pens over the past few months, and the listed timeframe is Month 4. The registry record does not give further information about questionnaire scoring, validation, or how incomplete responses were treated.

Confidence intervals and precision

In general, a confidence interval gives a range of values compatible with the observed data under the statistical method used. A narrow interval indicates greater precision than a wide interval, though precision does not establish that an outcome is important or free from bias. The primary endpoint description specifies a 95% Confidence Interval as its dispersion measure. No interval limits are reported in the registry record, so the precision of the primary percentage cannot be evaluated from that record.

Why crossover analysis needs care

In general, crossover data can depend on both the intervention used in a period and the order in which interventions were received. A participant’s experience in an earlier period might influence later perceptions, and responses may also change over time for reasons unrelated to the pen. Statistical methods can account for period and sequence structure, but the registry record does not state which model or test was used, whether a carryover effect was considered, or whether the primary result was analyzed as a within-participant comparison.

For a usability outcome, the response is also not a direct measurement of a biological quantity. It is a categorical choice about relative ease. A statistical analysis must respect those response categories and the paired nature of participants’ experiences if it uses both periods. The registry record reports the endpoint and its intended population but not enough method detail to identify the specific analysis or reproduce it.

Planning illustrations versus observed results

General sample-size planning uses assumptions about the effect to detect, the significance level, allocation, and the statistical approximation. Any planning illustration based on an observed effect is a hypothetical design calculation, not observed power and not evidence that a study was adequately planned. The registry record does not report the trial’s own sample-size justification or a statistical plan. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of the observed effect. They do not establish that those assumptions were the original design rationale.

For time-to-event outcomes, a planning calculation may count events, while other outcome types may use participants per arm. This study’s primary outcome is a percentage of responses, and the registry record identifies the outcome kind as not reduced to one comparison. The record does not provide a primary-outcome result from which a study-specific planning conclusion could be drawn.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 6 outcome measures, including the primary comparative usability outcome and secondary outcomes concerning preference, ease of use, intended pen choice, and ease ratings. When a study examines several outcomes, multiplicity can arise because repeated statistical tests or estimates create multiple opportunities to observe apparently notable findings. In general, a statistical plan may designate a primary endpoint, specify an order for testing, or adjust interpretation to account for multiple comparisons. The registry record does not report a multiplicity strategy, so it is not possible to determine whether any adjustment or testing hierarchy was used.

The record lists 1 analysis, but that count does not give the analysis method, the number of contrasts, or the handling of outcomes. The primary outcome result, its confidence interval, and any p-value are not reported in the registry record. Therefore, no conclusion about statistical significance or the relationship among outcome analyses can be drawn from the recorded information.

The primary analysis population is described as randomized participants who used a study pen at least once to administer somatropin. The analyzed number is defined as participants with evaluable data. This description does not provide the number with evaluable responses or explain whether all randomized participants were retained in the analysis. The number of participants with missing or unevaluable primary outcome data, reasons for missingness, and the method used to handle such data are not reported in the registry record.

In general, missing responses matter when the likelihood of providing an evaluable answer is related to a participant’s experience or response. Complete-case percentages describe those with evaluable data; they may not represent all randomized participants if the missingness is systematic. That is a general interpretive concern, not evidence that missingness was systematic in this study. The registry record does not report sensitivity analyses or imputation methods.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diarrhoea (0.8%), laryngitis (0.8%).

For the Safety Population, the registry record lists 120 participants at risk for serious adverse events and 2 participants affected. It also lists 120 at risk for other adverse events and 48 affected. These are separate registry categories and should be read as counts of participants, not as a measure of whether an event was caused by either pen. The record does not provide enough detail in these figures to establish causality or compare risk between the pens.

The top serious adverse event terms listed are Diarrhoea and Laryngitis, each reported as 0.8%. These terms describe the events recorded; their presence in the registry does not by itself establish a relationship to a device or treatment. The deaths field is not reported in the registry record.

Safety counts are distinct from the primary usability outcome. They do not answer whether participants found one pen easier to use, and the usability endpoint does not summarize adverse events. The record does not give further detail about event timing, severity beyond the serious-event classification, exposure by treatment period, or attribution. Those limits should be kept in mind when interpreting the safety figures.

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

The study’s stated purpose was to assess convenience and preference for the newly developed Mark VII pen compared with the current Genotropin pen among dyads and adult participants. Its randomized crossover design had participants use both pens in different sequences, and the primary question asked which pen was easier overall or whether there was no difference. These design features describe what the study set out to measure; they are not themselves evidence about which pen participants preferred.

The primary endpoint result is not reported in the registry record. There is no percentage for the combined response of no difference or easier use with the new pen, no reported confidence interval, and no category-level breakdown. It is therefore not possible to say from the registry record how participants’ answers were distributed or how precise an estimate would have been.

Even if a response percentage were available, the endpoint would need careful interpretation. Combining “no difference” and “new pen easier” does not show how many respondents found the pens equally easy and how many favored the new one. It also does not, on its own, describe the proportion who found the current pen easier. The secondary outcomes listed in the record address related but distinct questions, including preference and which pen participants would choose.

The outcome is a reported perception in an open-label study. It can describe what respondents said after using the devices, but it is not an objective measurement of device performance and does not establish a cause for a preference. The crossover format allows participants to experience both pens, while the order of use and possible effects of prior experience remain relevant to analysis. The registry record does not report how these design considerations were handled statistically.

Accordingly, the available record supports a description of the study question, design, and planned measurement, but not a conclusion about the observed comparative result. It also does not establish that either pen is better, worse, or equivalent. Such claims would require reported results and sufficient information to assess their uncertainty and analysis.

13. Why This Trial Matters Statistically

This trial is statistically distinctive because its main outcome is a participant-reported comparison in a randomized crossover design. Rather than assigning each participant to experience only one pen, the study assigned sequences in which participants used both. That structure can make paired experience relevant: a respondent can compare devices based on personal use. It also means that order and period are important elements of the design and may matter to the analysis.

The outcome definition illustrates how endpoint construction shapes interpretation. The primary measure groups reports that the new pen was easier with reports of no difference. Those are not identical experiences. A single combined percentage, even if reported, would answer a specific grouped question rather than fully describe preference across all available answers. Separate category results would be useful for distinguishing neutrality from a preference in favor of the new pen.

The study also highlights the relationship between study design and measurement. An open-label comparison of devices uses respondents’ perceptions in a setting where participants know which pen they are using. That is appropriate to describe as an unmasked usability assessment, while also recognizing that expectations may influence subjective reports. A statistical method cannot by itself remove all such interpretive concerns.

Finally, registry transparency is central to statistical interpretation. The record identifies the primary endpoint, the intended analysis population, and a 95% Confidence Interval as the dispersion measure, but does not report the endpoint estimate, interval, or detailed analysis method. Without those results, readers cannot assess the magnitude or precision of the response pattern. The distinction between a clearly stated statistical question and a reported statistical answer is important: the former is available in the record, while the latter is not.

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 record leaves several trial-specific limitations unresolved. It describes a crossover sequence and the timing of each pen period, but does not report whether the analysis accounted for period, sequence, or possible carryover of experience from one pen to the next. Those considerations can matter when participants compare devices after using them in a particular order.

The open-label design is relevant because the primary outcome was a subjective report of overall ease of use. Participants knew which pen they used, and the registry record does not describe procedures to limit or assess expectation effects. This does not invalidate the responses, but it affects what the responses represent: perceptions recorded in an unmasked setting.

The endpoint combines no difference with easier use for the new pen. This grouped measure does not preserve the distinction between an equal assessment and a favorable assessment. Although the registry lists secondary preference outcomes, their results are not reported in the registry record. The primary result itself, including its confidence interval, is also not reported.

The analysis population is described, but the number with evaluable primary outcome data and the handling of missing responses are not reported. The registry record also does not specify the statistical test or model, the multiplicity approach, or the trial’s sample-size justification. Enrollment of 120 should not be treated as the primary endpoint denominator or as proof of adequate precision. These omissions limit assessment of analysis choices, missing-data impact, and the strength of any comparative interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cross Over Convenience And Preference Study Of New Mark VII Compared To Genotropin Pen In Pediatric And Adult Subjects — NCT01112865.
• Registry record last updated 2012-05-22; status last verified 2012-05.
• Results first posted 2012-05-14.
• 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.

18. Record Summary

The registry record describes a completed, multicenter, randomized, open-label, two-arm crossover study of the Genotropin Mark VII pen and the current Genotropin pen. It lists Phase 3 and enrollment of 120 participants. The study concerned pediatric and adult participants with Growth Hormone Deficiency, including child-and-caregiver dyads.

Participants used the pens in one of two sequences, with each pen used for 2 months. The primary outcome asked at Month 4 whether the Mark VII pen was easier to use overall, the current pen was easier, or there was no difference. The endpoint focused on the percentage reporting no difference or easier use for the new pen, with a 95% Confidence Interval specified as the dispersion measure.

The registry record lists 6 outcome measures and 1 analysis. It describes the Full Analysis Set and Safety Population, but does not report the primary outcome estimate, its interval, the analyzed denominator, or detailed statistical methods. Safety counts include 2 participants affected by serious adverse events and 48 affected by other adverse events among 120 at risk in each category. Further interpretation is limited by the absence of reported endpoint results and analysis details.