December 3, 2018: FDA Calls for Comments on Proposed Rule to Allow Exceptions to the Requirement for Informed Consent in Minimal-Risk Research

The Food and Drug Administration (FDA) is proposing a rule to allow for a waiver or alteration of informed consent for clinical investigations posing no more than minimal risk to human participants. This rule would align FDA regulations with the Common Rule, reduce burden and costs for Institutional Review Boards, and be expected to lead to advances in healthcare.

“We expect benefits in the form of healthcare advances from minimal risk clinical investigations and from harmonization of FDA’s informed consent regulations with the Common Rule’s provision for waiver of informed consent for certain minimal risk research.” —  Federal Register /Vol. 83, No. 221

Currently, FDA allows a waiver or alteration of consent only in life-threatening situations. If aligned with the Common Rule, a waiver or alteration would be allowed if the IRB finds and documents that 1) the research involves no more than minimal risk, 2) the rights and welfare of subjects will not be adversely affected, 3) the research could not practicably be carried out without a waiver, and 4) the participants will be provided with additional pertinent information after completion of the trial.

Comments on the proposed rule are due by January 14, 2019.

November 13, 2018: Summary of Workshop on Pragmatic Trials of Therapeutic A vs B Interventions Now Available

The NIH Collaboratory recently convened a workshop to explore embedded pragmatic clinical trials comparing two or more therapeutic medical interventions. These “A vs B” trials are meant to test existing, viable treatment alternatives where there is uncertainty about which treatment is best in which populations. There are unique barriers that make these types of pragmatic trials especially challenging to implement. For the workshop, a panel of experts gathered to discuss challenges and solutions regarding partnering with healthcare systems to conduct the trials, unique legal and ethical issues, and design and operational considerations. The summary of the workshop is now available: Workshop Summary: Embedded Pragmatic Clinical Trials of Therapeutic A vs. B Interventions

 

Additional Resources:

Embedded pragmatic clinical trials of therapeutic A vs. B interventions workshop videocast.

 

October 12, 2018: MDEpiNet RAPID and SPEED Projects: Leveraging Real World Evidence to Get Better, Faster, Cheaper Medical Devices for Physicians and Patients (Renee Mitchell, MT, CLS, Terrie Reed, MSIE, Roseann White, MA)

Speakers

Renee Mitchell, MT(ASCP), CLS(NCA)
Regulatory Affairs
Boston Scientific Corporation, Inc.

Terrie Reed, MSIE
Senior Advisor for UDI Adoption
U.S. Food and Drug Administration (FDA)

Roseann White, MA
Director of Innovative Clinical Trial Statistics
Duke Clinical Research Institute

Topic

MDEpiNet RAPID and SPEED Projects: Leveraging Real World Evidence to Get Better, Faster, Cheaper Medical Devices for Physicians and Patients

Keywords

Medical devices; Real-world evidence; Medical Device Epidemiology Network; MDEpiNet; Unique device identifier; UDI

Key Points

  • In partnership, clinicians, device developers, and FDA can benefit from the use of real-world evidence on medical devices:
    •  Clinicians can contribute to the generation of real-world evidence.
    •  Device manufacturers can use real-world evidence to evaluate and release new devices and expand indications.
    •  Regulatory bodies can increase the use of patient-level data for device approval.
  • Unique device identifiers (UDIs) make it possible to follow medical devices longitudinally, advancing the quality of real-world evidence and allowing more sophisticated analyses.

Discussion Themes

The vision for the future is that registries will transform into big data solutions using multiple sources and will be more robustly integrated with electronic health records (EHRs). Both EHRs and registries will play a role.

More organizations as partners brings greater diversity, advancing better data and results. When stakeholders work together, learning curves can be accelerated toward a transformational approach to real-world evidence.

Tags

#MedicalDevices, #pctGR, @PCTGrandRounds, @Collaboratory1, @MDEpiNet_ppp

October 1, 2018: Meeting Minutes from NIH Collaboratory’s Regulatory/Ethics Core Discussions with the New Demonstration Projects

Meeting minutes and supplementary materials are available that summarize discussions related to the ethics and regulatory issues associated with each of the new UG3 Demonstration Projects. These discussions, which took place by teleconference, included representation from study principal investigators and study teams, members of the NIH Collaboratory Regulatory/Ethics Core, NIH staff, and NIH Collaboratory Coordinating Center personnel as well as some IRBs responsible for oversight of the projects.

May 1, 2018: Proposal for 6-month Delay for Implementation of Revised Common Rule

On April 20, 2018, the Department of Health and Human Services and 15 other federal departments and agencies proposed a rule to delay both the effective and compliance dates for the revisions to the “Federal Policy for the Protection of Human Subjects” (also known as the Common Rule). The Interim Final Rule initially announced a delay until July 19, 2018, and the new, proposed rule would delay by a further 6 months to January 21, 2019. This is intended to give institutions additional time to prepare to implement the revisions. Before January 21, 2019, institutions must comply with the pre-2018 Common Rule, except for these three proposed allowances, which are intended to reduce burden on regulated entities:

  1. Entities may use the 2018 definition of “research,” which deems certain activities not to be research,
  2. No annual continuing review is needed for certain categories of research, and
  3. Institutional review boards (IRBs) are not required to review grant applications related to research.

Comments on the proposal will be accepted until midnight EST on May 21, 2018, on the Federal eRulemaking Portal or through regular mail. To use the portal, search for “83 FR 17595” and click the box “Comment Now!”

March 15, 2018: New Resource for Understanding Ethical and Regulatory Architecture of Patient-Centered Outcomes Research Data

Using patient-centered outcomes research (PCOR) data requires balancing the need for sufficient private health information to support meaningful research with the need to protect patient privacy and autonomy. In support of this dual goal, The Office of the National Coordinator for Health Information Technology (ONC) has just released a document that provides a collection of tools and resources aimed at helping a broad audience of stakeholders understand the ethical and regulatory requirements related to collecting, using, sharing, and disclosing PCOR data.

“An architecture is necessary to ensure patient privacy is protected and health information is appropriately secured during collection, access, use, and disclosure as required by law, regulation, and/or policy.” —Legal and Ethical Architecture for PCOR Data

PCOR data will help expand the evidence base for therapies and improve health outcomes for individual patients.

Read the full document: Legal and Ethical Architecture for Patient-Centered Outcomes Research (PCOR) Data (“Architecture”)

The document is divided into 5 chapters:

Chapter 1: Overview of Legal and Ethical Architecture for PCOR Data provides background for the project and an overview of key ethical and regulatory requirements.

Chapter 2: Legal and Ethical Significance of Data for PCOR describes fundamental concepts for organizing data into categories such that legal and ethical frameworks can be applied. The chapter includes key considerations and types of data relevant to PCOR, such as clinical, administrative, patient-generated, etc.

Chapter 3: Linking Legal and Ethical Requirements to PCOR Data organizes the relevant legal provisions according to the key data considerations outlined in Chapter 2: identifiability, subject, source, access and use/purpose, consent/authorization, security, and legal status.

Chapter 4: Framework for Navigating Legal and Ethical Requirements for PCOR is designed as a decision tool that builds on the key data considerations described in Chapters 2 and 3. The goal of this chapter is to help researchers determine whether laws apply to particular data and if so, what requirements to attach to their collection and use.

Chapter 5: Mapping Research Flows to Legal Requirements identifies 6 hypothetical use cases, identifies decision trigger points, and maps representative data flows to the relevant legal requirements.

 

January 18, 2018: Implementation of Revised Common Rule Delayed

On January 17, 2018, the Department of Health and Human Services and 15 other federal departments and agencies announced a delay to both the effective and compliance dates for the revisions to the “Federal Policy for the Protection of Human Subjects” (also known as the Common Rule). Most provisions in the revised Common Rule were scheduled to go into effect on January 19, 2018. The Interim Final Rule announced a delay until July 19, 2018, with the option for further delay, to give institutions additional time to prepare to implement the revisions. Before July 19, 2018, institutions may only begin implementing provisions of the revised Common Rule that do not conflict with the pre-2018 Common Rule.

A notice of proposed rulemaking (NPRM) is also in development to seek public comment on a proposal for further delay in the required implementation of the revised Common Rule (for example, until January 21, 2019). A decision will be made after considering public comments.

November 20, 2017: NIH Collaboratory Core Working Group Interviews: Reflections from the Regulatory/Ethics Core

We recently asked Drs. Jeremy Sugarman and Kevin Weinfurt, Co-chairs of the Regulatory/Ethics Core, to reflect on the first 5 years of the Core as well as on the challenges ahead. The regulatory and ethical landscape for pragmatic clinical trials was not well defined when the Core began 5 years ago, and the Core helped to map and navigate the emerging landscape to enable the implementation of Demonstration Projects in ways that satisfied ethical and regulatory criteria.

“The Core’s work has led to the creation of a substantial body of scholarship contributing to the ongoing policy and ethics debates about pragmatic clinical trials.” – Drs. Sugarman and Weinfurt

Download the interview (PDF).

GCP Guidance and Pragmatic Clinical Trials: Opportunities for Harmonization

A new article published in Circulation by a group of authors from the Duke Clinical Research Institute describes tensions between pragmatic clinical trial design and Good Clinical Practice (GCP) guidelines, which were established in 1996 to help ensure the safety of participants in clinical trials and the validity of trial findings. Pragmatic clinical trials (PCTs) are designed to test interventions in real-world settings and populations rather than under highly controlled conditions, and thus rely on simplified procedures, such as those used for screening, informed consent, and participant follow-up.

The authors concede that many PCT features appear to be at odds with GCP guidance, which has arguably led to improvements in the consistency and quality of trial conduct. However, they also note data suggesting that the intensive approach to monitoring and documentation fostered by GCP may ultimately increase trial cost and complexity by emphasizing minutia that “may direct focus away from critical aspects of trial conduct.”

The authors go on to suggest that GCP guidance should be updated to account for a growing proportion of research that incorporates aspects of pragmatic trial design and is conducted with data gathered from electronic health records and registries. They also offer a path forward for pragmatic research under current GCP guidelines by outlining strategies for areas that include participant enrollment, monitoring, study visits, participant follow-up, and documentation.

The authors conclude that collaborative efforts from trial sponsors, regulators, clinical trialists, and patients will be necessary to realign the guidance with contemporary trial conduct while preserving its central goal of protecting trial participants.

For further information:

For additional reading:

Introduction to PCTs

eBook on PCTs (University of Colorado Denver)

Ethics and regulatory issues in PCTs articles

NIH Collaboratory PCT: Time to Reduce Mortality in End-Stage Renal Disease (TiME)

NIH Collaboratory PCT: Blood Pressure Medication Timing Study (BPMedTime)

PCORnet PCT: ADAPTABLE, the aspirin study

Clinical Trials Transformation Initiative Quality by Design Project

Clinical Trials Transformation Initiative GCP Training Project

 

New Lessons Learned Document Draws on Experiences of Demonstration Projects

The NIH Collaboratory’s Health Care Systems Interactions Core has published a document entitled Lessons Learned from the NIH Health Care Systems Research Collaboratory Demonstration Projects. The Principal Investigators of each of the Demonstration Projects shared their trial-specific experience with the Core to develop the document, which presents problems and solutions for initiation and implementation of pragmatic clinical trials (PCTs). Lessons learned are divided into the following categories: build partnerships, define clinically important questions, assess feasibility, involve stakeholders in study design, consider institutional review board and regulatory issues, and assess potential issues with biostatistics and the analytic plan.

Other tools available from the Health Care Systems Interactions Core include a guidance document entitled Considerations for Training Front-Line Staff and Clinicians on Pragmatic Clinical Trial Procedures and an introduction to PCTs slide set.