Adaptive Designs for Medical Device Clinical Studies

What You Need to Know? 👇

What is an adaptive design for medical device clinical studies?

An adaptive design is a clinical study design that allows for prospectively planned modifications based on accumulating study data without undermining the study’s integrity and validity. These modifications must be pre-specified in the protocol before study initiation.

When should I consider using an adaptive design over a traditional fixed design?

Consider adaptive designs when there’s uncertainty about key parameters like effect size or variability, when early stopping for success/futility is desirable, or when sample size reassessment could prevent study failure due to underpowering.

How do adaptive designs control Type I error rates?

Adaptive designs control false positive rates through pre-specified statistical adjustments that account for multiple looks at data, sample size modifications, or other adaptations. Methods include alpha-spending functions, conditional power calculations, and Bayesian approaches.

What are the main challenges in implementing adaptive designs for medical devices?

Key challenges include maintaining operational bias control through proper blinding/firewalls, managing logistical complexities, ensuring adequate DMC oversight, obtaining IRB approvals for modifications, and preventing information leakage that could compromise study integrity.

Do I need FDA approval before implementing an adaptive design study?

Yes, sponsors should engage FDA early through pre-submission meetings to discuss adaptive design plans. For significant risk devices, the adaptive protocol must be approved through the IDE process before study initiation.

Can adaptive designs be used for open-label medical device studies?

Yes, but with extra caution due to increased operational bias risk. Pre-specification of all adaptations is paramount, and detailed procedures must prevent unplanned modifications based on interim findings that could compromise scientific validity.

---

What You Need to Do 👇

Recommended Actions

1. Determine if adaptive design is feasible and advantageous for your specific study
2. Develop detailed prospective plan for adaptations including:
   • Statistical analysis plan
   • Operating characteristics
   • Decision rules
   • Monitoring procedures
   • Firewall implementation
3. Establish appropriate oversight including:
   • Data Monitoring Committee if using unblinded data
   • IRB review procedures
   • Monitoring plan specific to adaptive aspects
4. Engage with FDA through pre-submission process to discuss adaptive design strategy
5. Document thoroughly:
   • Adaptation implementation
   • Maintenance of study integrity
   • Data before and after adaptations
   • Any deviations from planned adaptations
6. Implement robust infrastructure for:
   • Data management
   • Information access control
   • Communication procedures
   • Supply chain management
7. Prepare final study documentation including:
   • Description of adaptation implementation
   • Complete datasets
   • Pre-specified statistical analyses
   • Documentation of any deviations

Key Considerations

Clinical testing

• Adaptations must be prospectively planned and described in protocol before study initiation
• Changes based on unblinded data require careful planning and statistical considerations
• Need to control Type I error rate and maintain adequate power
• Need to assess homogeneity of results before and after modifications
• DMC oversight recommended for adaptive designs using unblinded data

Safety

• Adaptive designs can be used for safety endpoints
• Early stopping rules for safety can be incorporated
• DMC should monitor safety throughout adaptive trials

Other considerations

• Need robust infrastructure to implement adaptive designs appropriately
• Must minimize operational bias through firewalls and blinding procedures
• IRB oversight and informed consent must reflect adaptive nature of study
• Detailed documentation of adaptation implementation required
• Pre-submission interaction with FDA recommended
• Need monitoring plan focused on adaptive design aspects

---

Relevant Guidances 🔗

• Design Controls for Medical Device Manufacturers
• Design Considerations for Medical Device Pivotal Clinical Studies
• Statistical Guidance for Reporting Diagnostic Test Results with Qualitative Outcomes
• Bayesian Statistics in Medical Device Clinical Trials: Design, Analysis and Implementation

Related references and norms 📂

• ISO 14155: Clinical investigation of medical devices for human subjects - Good clinical practice

---

Original guidance

• Adaptive Designs for Medical Device Clinical Studies
• HTML / PDF
• Issue date: 2016-07-27
• Last changed date: 2020-10-20
• Status: FINAL
• Official FDA topics: Medical Devices, Good Clinical Practice (GCP), Premarket Approval (PMA), Premarket, Biologics, HUD/HDE, Investigational Device Exemption (IDE)
• ReguVirta ID: a9d7a8cd59dc49fe20444b10b3191a8d