Regulatory Science Virtual Symposium: “Make Informed Decisions: Key Statistical Principles to Clinical Trial Design” Session 3: Designing Medical Devices (2022)

1. When do we do device trials?
   1. Device trials are conducted for about 15% of approved devices
      1. Only when the information is necessary to prove safety/efficacy that performance testing, animal testing, and previous literature cannot
      2. Clinical studies are not conducted for devices such as surgical scissors
2. Typically, device trials are done on implants
   1. Restraints include device costs, ethics, study controls, device size
   2. Post-market trials are often conducted for reimbursement and expansion of device knowledge
3. Strong partnerships are needed
   1. Include hospital administration, radiologists, therapists, patients and their families, other clinicians, R&D teams, and committees etc.
4. Transcatheter versus transapical implants
   1. Threading through a femoral artery is as good as going through the heart – Will patients still do as well?
   2. Complex design: prospective, non-blinded, randomized, controlled, multi-center clinical trial with non-inferiority outcome
      1. Based on patients who can get access through transfemoral vs transapical groups
      2. Each group got randomized
      3. Primary safety/Effectiveness endpoint: As time went by, some patients in both groups died but note that the death rate for transfemoral route was slightly less
      4. Non-inferiority study: we are good as within a 75% range and outcome measures of 3 months
   3. Can be challenging to pre-specify in device trial so industry has adopted adaptive trial design
5. Adaptive trials                
   1. Design that “allows for prospectively planned modification based on accumulating study data without undermining the study’s integrity and validity”
   2. Factors that might be modified when following this type of design:
      1. Number of patients
      2. Patient population
      3. Randomization
      4. Primary hypothesis
      5. Decision rules
   3. Some advantages of Adaptive Trials include reduced duration, enrichment of the experiment arm, and use of control group from another trial, sample size adjustment
   4. Adaptation usually determined by stages of endpoints
   5. Some disadvantages include potential for damaging statistical validity, affecting bias of clinical managers, and requires predictions prior to approval
   6. CDRH experience
   7. As precision medicine becomes more common, more studies will use adaptive design
6. Let us look at a pressure-ulcer trial using microstimulators
   1. Bions and insertion tool
   2. Inclusion criteria
   3. History
   4. Typical exercise program
7. Another Study: Shoulder Subluxation
   1. An example of historical controls
   2. Measures of muscle thickness using ultrasound
   3. Takeaway: Want to use robust outcome measures
8. Registries versus trials
   1. Real world data is a rich source of information
   2. Types of registries: patient, specialty, population, device, and payer
   3. Harder to control bias and apply statistical analyses from data taken from registries
9. Questions?

Accompanying text created by Annie Ly | RKS Project Administrator, SC CTSI  lyannie@usc.edu