Quantics has a long history

of supporting clients with statistical aspects of medical device trials

Study Design

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Interim Safety Analysis

Interim Safety Analysis

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Independent Protocol Review

Independent Protocol Review

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Independent Statistical Analysis Review

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Sample Size Calculation

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Final Study Reporting

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Adaptive Design

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Regulatory Submission Support

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Study Design

Quantics is very experienced in many different types of study design, in many different clinical areas with a specialisation in both invasive and noninvasive medical device trials 

We can provide a report on the pros and cons of particular designs including adaptive models and other complex designs to ensure that the trial gains the maximum information at minimum cost.

Project Insight

Quantics reviewed a draft protocol for a new wearable device. The manufacturer had included many subgroup analyses for the secondary endpoints, in the belief that these would be important for licensing submission.

Quantics advised that subgroup analyses for secondary endpoints are often not required by regulators, and with small sample sizes proposed could produce very misleading results. Based on this advice, the client reviewed the study protocol of the predicate device, found that this study had not included subgroups, and removed these analyses from their protocol. This substantially reduced the costs and time required for the data management and statistical analyses.

Sample Size Devices

Sample Size Calculation

Sample size calculations are vital to clinical trials.  Too big a sample wastes time and money, but reducing the number too far may result in the entire trial being wasted.

Sample size calculations are based on a set of assumptions about what the trial is expected to show, based on historical data. Quantics has extensive experience in this field, and can provide a comprehensive report on the impact of varying the assumptions on the sample size and likely trial success, enabling you to balance the risk of trial failure against cost and recruitment time. We can explain the options with risks and consequences in ways suitable for scientists and financial supporters.

We have experience to help you in all of the following areas:

Exploratory studies / descriptive studies

Non-inferiority or superiority studies

  • Choice and justification for non-inferiority margin

Adaptive designs

Designs involving data monitoring committees and interim analysis

  • Impact of data monitoring committee decisions or interim analyses  on sample size (power) of the study – does it need to be modified?
  • Stopping rules

Hidden Consequences of Interim Analyses & Adaptive Trial Options

Interim analyses are common in medical device trials for a variety of reasons. Just having a look is fine, but if the outcome  of the analysis could change the conduct of the trial, for example by early stopping for superiority, futility or safety,  then there is a problem. If the analysis result does stop the trial, then all is well, but if the analysis does not show that the trial can be stopped early, then the fact of having undertaken the analysis might undermine the power of the trial to demonstrate the objective when the trial is finally complete.

READ OUR BLOG ON THIS SUBJECT

Adaptive Design

If there is not enough historical evidence about the expected performance of a clinical trial to be reasonably confident in the design, an adaptive trial can be designed. An adaptive trial monitors the outcomes of interest as the trial progresses, and uses this information to adjust trial parameters such as sample size, prescribing schedule, doses used, or patient selection criteria.

If this is to be done, the adaptive process MUST be fully defined in the protocol prior to the trial start and can not be subsequently changed.

Details of the adaptive process  need to be masked from investigators to maintain blinding and Quantics, as an independent statistical consultancy, can design, monitor analyse and direct changes for an adaptive trial without risk of un-blinding.

Devices Interim Analysis decision tree 2
Interim-Safety-report

Interim Safety Analysis

Interim analyses and data monitoring committee meetings need to be planned and defined in the SAP. In particular it is important to define what data is to be reported, whether it is to be unblinded, and how the consequences of any decisions made will be implemented, and what the implications may be on the power of the study and required sample size.

Quantics can provide completely independent analysis, allowing unblinded results to to be examined without risk of unblinding of investigational staff. Quantics staff can also be part of the review group if required.

Independent Review

Quantics can provide a completely independent review of CRO proposals to address your core concerns:

  • Is the overall study design appropriate for the objectives?
  • Is the protocol sufficiently consistent and well specified to allow results to be calculated without ambiguity?
  • Is the SAP consistent with the protocol and are the techniques proposed appropriate?
  • Does the SAP specify management of special aspects such as population groups, missing data?
  • If a data monitoring committee or interim analysis is planned,
    • Are the requirements specified?
    • Has management of consequent decisions been specified?
  • Does the CRF capture the information required for the analysis?
  • Is the information captured by the CRF in the most efficient form for the analysis?
Clinical Trial Independent checklist

Meeting Representation

We are happy to represent you at face to face meetings if required.

Regulatory Submission Support

Quantics has extensive experience discussing statistical issues raised in the design stage or at NDA stage with regulators including MHRA,FDA, EMA, PMDA.