Global Regulatory Pulse

Three Essentials for Smart IVD Clinical Trial Design

In Consulting by Ben Brown, PhD, Michelle Young, MBT and Christopher Zurenko

When designing an In Vitro Diagnostic (IVD) clinical trial, there are three major areas that must be considered if manufacturers are to achieve optimal, accurate outcomes:

  • Biostatistics
  • Clinical research conduct
  • Data management

While these three clinical research disciplines are interdependent on one other, equal attention should be paid to each of these functions, as outlined below.

I. Biostatistics

The area of Biostatistics plays a critical role in achieving IVD clinical trial success, much of which is dependent on compiling evidence to effectively bring a product to market. Other considerations include:

  • IVD studies should be designed in accordance with guidance documents that are applicable to a particular manufacturer’s IVD product, and based on target condition and region—all of which are critical for accounting for each facet of a diagnostic.
  • It is suggested that the clinical trial Biostatistician work closely with the Clinical Study Manager to ensure that the population of interest is being successfully enrolled into the trial.
    • Reasons to exclude data should also be pre-specified to mitigate bias.
  • It should also be required that the Biostatistician collaborate with the Data Manager to ensure all necessary endpoints and covariates are being collected.
  • It is also important that the assigned Biostatistician ensures that the study, and any subgroup analyses, is adequately powered by determining the following requirements:
    • Sample size
    • Proper statistical methods
    • Results that are formatted properly for the intended regulatory authority

II. Clinical Research

Clinical research conduct requires effective trial management regardless of size, duration and complexity of a clinical trial. Many trials fail due to poor design, lack of documentation, inefficient data analysis, and the inability to support trial endpoints.

As such, a Clinical Study Manager plays a critical role in the trial design, planning and execution of a successful clinical study. For IVD trials, there are various clinical trial designs, such as procurement, method comparison, and reproducibility studies, which seek to answer various questions regarding the safety and efficacy of an IVD product. Also noteworthy is the fact that clinical trial results may influence physicians’ treatment plans or a patients’ decisions regarding healthcare options.

It is recommended that the clinical research phase should consider input from other disciplines, such as the Biostatistician, to determine:

  • Trial sample size
  • Number of trial sites needed
  • Data management approach (to determine what data and how data will be collected)

Additionally, it is critical that:

  • The Clinical Study Manager design a well-structured trial protocol, with a clear objective to capture study endpoints and to support the intended use of a particular IVD product.
  • Site selection is carefully considered, as it greatly affects design and identification of a study’s target subjects for enrollment and sample collection.

As a trial progresses, frequent monitoring of clinical procedure results can also ensure timely collection of quality data to support study claims for IVD regulatory approval in varying geographies.

III. Data Management

Data is the primary focus of any clinical trial and proper management of this information can make or break the overall outcome.

The clinical study Data Manager must work closely with nearly every stakeholder involved in a study to help ensure that database specifications are met, users can seamlessly navigate the Electronic Data Capture system (EDC) and the integrity of the data being captured is maintained.

This requires a collaborative and interactive relationship between Data Management, Biostatistics, Clinical Affairs and study sites while developing the key data collection documents such as the:

  • Data management plan
  • Centralized data monitoring plan
  • Case report forms (CRFs)

Careful consideration should also be paid when building a trial database and managing all aspects of the EDC—once active—as IVD studies present a unique challenge in terms of captured data type and volume

EDC customization, utilization of templates for IVD-specific trials and leveraging past experience with IVD trials can prove helpful in reducing development timelines, enhancing efficiencies for more productive data entry and decreasing training time for future IVD trials. (The functionality of an EDC should be maximized to perform efficient, and in some cases automated, monitoring to ensure that all data is accurately collected. Custom dashboards should be used to provide real-time enrollment metrics to track the progress of a trial.)

How Can NAMSA Help?

Getting your IVD innovation to market…faster.

NAMSA is a leading contract research organization (CRO) and the world’s only Medical Research Organization (MRO) that assists In Vitro Diagnostics (IVD) manufacturers translate great ideas into great medical products.

From point-of-care diagnostics to instrument platforms to companion and complimentary devices, NAMSA provides global expertise for the full product development continuum. Through our regulatory consulting, laboratory testing and clinical research services, we consistently deliver proven time savings and cost efficiencies to clients around the world, resulting in hundreds of successful IVD regulatory submissions.

Learn more about NAMSA’s IVD services here…or, check out our latest on-demand webinar, “IVD Clinical Trials: Essentials of Effective Product Launch in 2019 and Beyond.

Authors:

Ben has been in the medical device industry for seven years and is known for his collaborative strength in incorporating biostatistical strategy into clinical research setup, execution and data management that results in precise reporting to support market approval. Ben completed his Ph.D. from the University of Minnesota, where he was a clinical trial research assistant for an HIV treatment. His dissertation focused on developing machine learning methods to perform signal detection in high dimensional data with correlated outcomes and variables measured with error. Ben also holds a B.A. in mathematics with a concentration in statistics from St. Olaf College, where he now serves as an Adjunct Assistant Professor of Statistics. Mr. Brown has completed several industry trainings, including Good Clinical Practices, SAS Macro Language 1, SAS Programming Essentials 1, and SAS Programming Essentials 2. His personal affiliations include the American Statistical Association and the International Biometrics Society.

Michelle has 20 years’ experience in clinical research and expertise within all stages of IVD studies – study design, protocol development, site initiation, clinical study management, project management, resource management, on-site / remote / risk based monitoring, and site closeout. She was the lead CRA for clinical IVD cardiovascular, Alzheimer’s, and lung cancer studies resulting in 510(k) and PMA submissions and managed internal employees and external partners for companion diagnostic study while working for a global IVD manufacturer. Michelle has been with NAMSA for over six, and most recently started focusing on IVD studies. She has also worked for industry leaders Roche Molecular Systems as Principal Clinical Research Associate, Align Technology, Boston Scientific, and Eclipse Surgical Technologies. Michelle is a graduate of San Jose State University where she obtained a Master’s Degree in Biotechnology and also University of California, Davis where she was awarded a Bachelor of Science in Psychobiology. Michelle is a member of the Association of Clinical Research Professionals (ACRP), Healthcare Businesswomen’s Association (HBA), and Toastmasters International.

Chris has over 18 years’ experience in research and development within the pharmaceutical and biotechnology industries. Prior to joining NAMSA, he spent over four years with Thermo Fisher Scientific in R&D related to their IVD product offerings. Throughout his career, he has been part of teams that have brought products such as LYRICA®, SELZENTRY®, and Oncomine™ Knowledgebase Reporter to market, and has successfully contributed to several publications appearing in top tier journals. Chris joined the IVD group at NAMSA in 2018 to further his career in the IVD space. He holds a Bachelor’s of Science in Biology from Central Michigan University, a Master’s of Science in Medical Informatics from Brandeis University, as well as certificates in medical writing, medical terminology and clinical trial design. He is an active member of the American Medical Writers Association and the Society of Clinical Data Management.