June 1, 2021

This document is intended to serve as a study design blueprint for analytical validation of IVDs using capillary whole blood specimens collected by fingerstick, herein referred to as “fingerstick” or “FS” specimens.

This document provides general guidance on considerations for study design. Considerations for specific devices may require modifications to implement these studies.

Reading and following this document does not guarantee either FDA approval/clearance or payment from insurance companies.

The Blueprint is organized into seven key sections:

  • Section One: Introduction introduces the scope of the Blueprint, provides key definitions and explanation of acronyms, and reviews regulatory considerations of point of care testing (POCT) devices.
  • Section Two: Study Designs for Candidate Device Clearance/Approval as a Non-Waived Test reviews design considerations including collection and testing sites and operators, overall study design for FS and FS and venous whole blood (WB) specimens, and detailed considerations for method comparison studies and precision studies.
  • Section Three: Study Designs for CLIA Waiver Application for the Candidate Device reviews design considerations including collection and testing sites and operators, as well as the sequential and dual approaches for CLIA waiver studies for non-waived and new devices, respectively.
  • Section Four: Considerations for the Use of Surrogate Samples outlines design considerations for method comparison studies and precision studies that use surrogate samples.
  • Section Five: Considerations for Data Analysis in Method Comparison Studies discusses over sampling in method comparison studies and considerations for data analysis, including visual presentation of data, regression analysis, and bias at medical decision levels (MDLs).
  • Section Six: Considerations for Data Analysis in Precision Studies reviews components of variability and considerations for visual presentation of precision study data.
  • Section Seven: Additional Considerations for Precision Studies with Fingerstick (FS) Specimens reviews additional precision study design considerations not covered earlier in the Blueprint.
April 5, 2021

There are key distinctions between device trials and drug trials that present unique opportunities, challenges, and resource needs for engaging patient insights in the device field. In developing this report, the Science of Patient Input (SPI) Participation in Clinical Trials Working Group of the Medical Device Innovation Consortium evaluated a series of device trial characteristics (level of invasiveness, outcomes assessment, trial enrollment, and trial design) and prioritized them based upon their relevance for patient engagement.

It is hoped that this report provides a concise set of considerations for medical device developers to evaluate as they pursue patient engagement in their clinical trials and product development activities. Recognizing that this work is complex and made increasingly so by the heterogeneity of the device development landscape and understanding that no single compilation of information can provide everything a sponsor would need, the resources presented within this report are offered as a foundation from which sponsors can advance their efforts to generate and incorporate patient input into trial design and conduct.

March 17, 2021

This document provides an updated Literature Review for the Medical Device Innovation Consortium (MDIC) Science of Patient Input (SPI) Working Group for submission as a deliverable under the MDIC Broad Agency Agreement (BAA) contract.

This high-level review reflects a broad scan of publicly available information about relevant organizations, initiatives, materials, and publications.

While it is up to date as of December 2020, this summary is not exhaustive and should be viewed as a representative snapshot of activities and resources within the highly active and evolving field of patient engagement in clinical research. As new organizations, resources, and publications are being developed and launched continually, this work should be updated regularly to ensure its completeness and relevance over time.

March 8, 2021

The Medical Device Innovation Consortium (MDIC) Virtual Patient Engagement Forum held on November 18, 2020, engaged approximately 100 participants, including patients, patient advocates, medical device leaders, regulators, healthcare providers, payers, and experts in communication and shared decision-making. Participants joined in a day-long, interactive meeting focused on communicating benefit-risk and uncertainty for medical devices. Content for the Forum included presentations, panel discussions, and interactive activities inspired by the best practices and examples contained within the recently released MDIC Best Practices for Communicating Benefit, Risk, and Uncertainty Report.

Overall, this event offered the medical device community a platform from which to evaluate current communications efforts, identify gaps, and prioritize additional needs for advancing progress on this topic. Key lessons learned and themes emerging from the Forum provide the foundation for this report.

March 2, 2021

As part of the Science of Patient Input (SPI) Initiative to develop a Framework for Patient Input in Medical Device Clinical Trials, the Medical Device Innovation Consortium (MDIC) conducted three surveys and one set of telephone interviews to compile information about patient engagement activities among device and diagnostic industry stakeholders, individuals identifying as patients, and a select group of medical device study investigators. Collectively, the information gleaned from these three surveys provides detailed perspectives on patient engagement during clinical research from key stakeholders in medical device clinical trials. This information will also be incorporated into the MDIC’s report on Maximizing Patient Input in the Design and Development of Medical Device Clinical Trials.

In 2018, MDIC surveyed 53 device and diagnostic industry stakeholders and separately surveyed 123 individuals identifying as patients. The goal of the complementary surveys was to inform future work to develop guidelines for industry on how to involve patients in the design of clinical trials. For the third survey in 2020, we focused on investigators who received research funding from the Patient-Centered Outcomes Research Institute (PCORI) because PCORI requires investigators to engage patients and other stakeholders in their study.

February 17, 2021

Emerging HealthTech Series: Case for Quality

Learn more about Case for Quality through Emerging HealthTech’s six-part series covering the following topics:

  • Clip 1: The Genesis of Case for Quality
    • What Case for Quality is and what it aims to accomplish as a collaborative community
  • Clip 2: Quality as a Journey for the Patient
    • A widening of perspective – from product quality to the broader quality for the patient
  • Clip 3: The Culture of Quality
    • What is a Culture of Quality, why it is important and what it means to the medical device industry and, ultimately, patients
  • Clip 4: Why Should Companies (Large & Small) Engage in Case for Quality
    • These are just some of the unique benefits of participating in Case for Quality, especially for smaller companies and emerging technologies
  • Clip 5: Can Corrective and Preventive Action (CAPA) Be Cool?
    • Yes it can! Learn about Case for Quality’s “Make CAPA Cool Pilot Study” and how it can improve how your company performs CAPA.
  • Clip 6: The Digitalization of an Expanding Medical Device Industry
    • A new direction in the medical device industry toward using advanced technologies, including digital predictive methods and models, and algorithmic approaches to quality management systems and product quality to drive better patient outcomes.
February 9, 2021
  • Domestic or Outside the U.S. Manufactures marketing devices in the U.S.
  • Must have an established QMS in accordance with 21 CFR Part 820.
  • Manufactures meeting the following test case scenarios:
    • 2+ Voluntary Self-Reporting Manufacturers* – The manufacturer is self-identifying major deficiencies with the Quality System regulation as defined in the Compliance Program 7382.845.
    • 2+ Manufacturers* that received an FDA 483 during a recent inspection – The manufacturer has major deficiencies with the Quality System regulation as defined in the Compliance Program 7382.845 observed during an inspection; with no advisory action by FDA (e.g. WL, UL) or Regulatory Meeting as defined in Chapters 4 and 10 of the Regulatory Procedures Manual.
    • 2+ Manufacturers* where Agency has issued an Advisory Action or Requested a Regulatory Meeting – Manufacturer with open Warning Letter, Untitled Letter, or Regulatory Meeting as defined in Chapters 4 and 10 of the Regulatory Procedures Manual.

Note: Sites with a Consent Decree are not eligible for this pilot study. See 820.3(o) for definition of a manufacturer

Apply here.

A Site’s enrollment will be kept confidential unless it provides permission for its participation in the pilot study to be made public. This option must be selected on the application form linked to the MDIC Site.

MDIC will notify the Site that it was not accepted. It is recommended that applicants should continue engaging as they normally would with the Agency.

There is an escalation process built into the pilot process. The Site would notify the MDIC Case for Quality Program Manager (dsteele@mdic.org) that it cannot meet the expectations. If no path forward can be identified, the Site will be removed from the pilot, and engagement with the Agency will follow its normal process.

There is an expectation that the Site will engage fully in the pilot study, this includes the CMMI appraisal, residual risk analysis, action plan, quarterly checkpoints, performance metrics, and FDA follow-up inspection (if applicable).

• CMMI must be used for the Appraisal and Mgmt-Ctrl must be used for the residual risk assessment tool.

Additionally, regular lessons learned sessions, participant surveys, and pilot study data collection activities will be completed with the Site
The Site will be enrolled in the pilot study for approximately 18 months after application approval.

• Specific sites could take longer to close compliance gaps and /or improvements identified as a part of this pilot. However, pilot data collection will end after 18 months.

The on-site CMMI Appraisal is typically 5 days, with additional time required for planning and post-appraisal activities as needed.

• Appraisal Planning Activities could require 3-5 days for a small number of site resources.

A Site does not have to respond to all identified CMMI and/or Residual Risk tool gaps. It should take all the data provided by the pilot to create an improvement action plan in a way that positively impacts the closure of their compliance gaps and the sustainability of impacted processes.

The cost of the pilot is covered by MDIC. If the Site decides to further engage with Mgmt-Ctrl beyond the residual risk assessment tool or enrolls in a follow-up CMMI appraisal, the Site must cover the cost of this additional work.

MDIC will cover the costs of the CMMI Appraisal and other activities conducted under the pilot. This includes the development of an action plan that is agreed upon with FDA, and that is intended to address any FDA inspectional observations, concerns communicated in FDA advisory actions, CMMI appraisal gaps, and residual risk assessment concerns.

During the pilot study, the FDA intends to forgo planned routine inspections for participating manufacturers; however, the agency intends to continue to conduct “for cause” inspections of such manufacturers as necessary and appropriate. Participants will have the opportunity to complete the improvements to product quality and safety as specified on their action plan.

Additionally, the participating manufacturer may request a Certificate for Foreign Governments (CFG), if needed. The participating manufacturer may request a Certificate of Foreign Governments (CFGs) consistent with the Process to Request a Review of FDA’s Decision Not to Issue Certain Export Certificates for Devices. If the participants request a CFG, they are encouraged to engage with the CDRH’s Case for Quality team caseforquality@fda.hhs.gov and the Exports Team within CDRH’s Office of Regulatory Programs (ORP), Division of Establishment Support using exportcert@cdrh.fda.gov.

The pilot study process was intentionally defined in partnership with both ISACA (i.e., representatives of the Appraiser community) and FDA. Industry, Mgmt-Ctrl, ISACA, CDRH, ORA, MDIC

The purpose of this pilot study is to evaluate the effectiveness of the CMMI Appraisal model and the Mgmt-Ctrl residual risk tool at aiding a site in its journey towards compliance and a culture of continuous improvement. Information shared with CMMI Appraisers and Mgmt-Ctrl would remain confidential as maintained by formal agreements with the site.

During the pilot study, the FDA intends to forgo planned routine inspections for participating manufacturers; however, the agency intends to continue to conduct “for cause” inspections of such manufacturers as necessary and appropriate. Participants will have the opportunity to complete the improvements to product quality and safety as specified on their action plan.

FDA intends to confirm the adequacy of the corrective actions taken to address the previously cited observations and/or violations through a follow-up inspection. Specifically, FDA intends to conduct an inspection after the MDIC ASC Pilot Study activities have been completed.

• Following the pilot, the Agency intends to follow its normal processes when creating the work plan and determining when the manufacturer will be inspected.

If the follow-up inspection observes major deficiencies as noted on section A,1 of part V, regulatory/administrative follow up of “Compliance Program Guidance Manual; Inspection of Medical Device Manufacturers” FDA intends to follow the traditional pathway to engage with the manufacturer. If this situation does occur, the MDIC ASC Working Group intends to engage with the manufacturer to learn more about what could have been done better and whether there was a need to add additional PA’s into the appraisal process or engage differently with the manufacturers.

Once a state of compliance has been achieved and the adequacy of the corrective actions is verified through FDA inspection; the Site may seek enrollment into the CfQ VIP program once the program becomes operational, and if the enrollment criteria for the CfQ VIP pilot program have been met.

Enrollment Criteria Link (ISACA Website): https://cmmiinstitute.com/medicaldevice#MDDAP_Program_Requirements
Pilot Study Application Link (MDIC Website): https://mdic.org/project/case-for-quality-accelerate-sustainable-capability-pilot/

The ASC pilot study is facilitated by MDIC; FDA and other stakeholders are contributors to this MDIC effort. It leverages learnings from the Case for Quality Voluntary Improvement Program (VIP), but it is a separate activity. Enrollment on the ASC pilot is voluntary and would not preclude the site from enrolling in other pilots or programs (e.g., MDSAP).

January 19, 2021

A culture of quality in life sciences organizations transcends compliance and serves as a clear, competitive differentiator. In an industry facing increasing competition, regulations, and customer demands, and a mandate for innovation, today’s life sciences leaders are committed to cultivating a culture of quality.

Driven by payers (including the Centers for Medicare and Medicaid Services), the life sciences industry is moving from a reactive to a proactive approach to quality. This requires, in part, a commitment to measuring quality investments. Life sciences organizations, more and more, are being measured and paid based upon clinical outcomes and the quality of their products and services.

This playbook, developed by the Case for Quality Collaborative Community, describes 10 best practices for moving from a culture of compliance to a culture of quality:

  1. Facilitate a Culture of Quality
  2. Develop a Quality Strategy
  3. Make Quality a Priority
  4. Measure the Value of Quality
  5. Be Proactive, Not Reactive
  6. Clearly Define Quality at the Individual Level
  7. Encourage Quality Behaviors
  8. Use Quality Benchmarking
  9. Use Quality Metrics
  10. Recognize and Reward Quality
January 14, 2021

The objective of this pilot study is to leverage a quality system maturity and integration approach to provide manufacturers with systemic insight that may improve the effectiveness of the quality system; focus and accelerate improvement efforts to reach a state of sustainable compliance faster; structure systems for continuous improvement; identify objective performance metrics, and develop reports that may provide the agency with the information it needs to oversee product safety throughout the pilot process.

To encourage manufacturers to enroll and participate, this pilot study will cover the costs of the activities listed and defined in this playbook.