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Interventional Cardiology Podcast: Optimizing the Use of Implantable Devices to Treat Heart Failure Patients
A growing number of implantable devices provide patient information that can lead to improved outcomes and health. So how can these devices support the treatment of heart failure patients?
Manesh Patel, MD, Associate Professor of Medicine and Director of Interventional Cardiology at Duke, and Kishan Parikh, MD, Cardiology Fellow, explore this question in the latest DCRI Evidence to Practice Series podcast. Their discussion focuses on the CHAMPION trial published in the November 2014 issue of Circulation: Heart Failure.
This is the third of eight monthly Interventional Cardiology podcasts supporting the DCRI’s education mission to accelerate the adoption of research to practice.
On June 21, NIH published in the Federal Register the “Final NIH Policy on the Use of a Single Institutional Review Board for Multi–Site Research.”
The NIH found “no compelling reason” to narrow the essential scope of the final policy—it will cover all domestic sites of NIH-funded non-exempt multi-site studies as was proposed. However, the final policy clarifies the policy intent and modified several provisions.
The final policy will not take effect until May 25, 2017. In the interim, the NIH will issue guidance and provide resources to assist awardees in adapting to the shift.
This policy establishes the expectation that all sites participating in multi-site studies involving non-exempt human subjects research funded by the National Institutes of Health (NIH) will use a single Institutional Review Board (sIRB) to conduct the ethical review required by the Department of Health and Human Services regulations for the Protection of Human Subjects at 45 CFR Part 46.
The policy applies to the domestic sites of NIH-funded multi-site studies where each site will conduct the same protocol involving non-exempt human subjects research, whether supported through grants, cooperative agreements, contracts, or the NIH Intramural Research Program. It does not apply to career development, research training or fellowship awards.
Foreign sites participating in NIH-funded, multi-site studies will not be expected to follow this policy
Multi-site studies within ongoing, non-competing awards will not be expected to comply with the policy until a competing renewal application is submitted.
Applicants/offerors will be expected to submit a plan identifying the sIRB that will serve as the IRB of record for all study sites in the applications/proposals they submit to the NIH. The NIH’s acceptance of the submitted plan will be incorporated as a term and condition in the Notice of Award or in the Contract Award.
It will be the responsibility of the applicant/offeror to assure that the sIRB is qualified to serve; the applicant’s plan will not be evaluated in peer review.
If, in delayed-onset research, an sIRB has not yet been identified, applications/proposals should include a statement that awardees will follow this Policy and communicate plans to use a registered IRB of record to the funding NIH Institute/Center prior to initiating a multi-site study.
The additional costs associated with sIRB review may be charged to grants or contracts as direct costs, provided that such costs are well-justified and consistently treated as either direct or indirect costs according to applicable cost principles in the NIH Grants Policy Statement and the Federal Acquisition Regulations (FAR) §§31.202 and 31.203.
Responsibility of Awardees
Awardees are responsible for ensuring that authorization agreements between IRBs (also called “reliance agreements”) are in place; copies of authorization agreements and other necessary documentation should be maintained in order to document compliance with this policy, as needed. As appropriate, awardees are responsible for ensuring that a mechanism for communication between the sIRB and participating sites is established.
Awardees may delegate the tasks associated with these responsibilities.
Responsibility of Funding Institute/Center
Funding ICs are responsible for management and oversight of the award, including communicating with the awardee regarding the implementation of its proposed plan to comply with the sIRB Policy. In the event that questions arise about the awardee’s plan, including the IRB that has been selected to serve as the sIRB, the funding IC will work with the awardee to resolve them.
Exceptions to the policy will be granted if the use of an sIRB is prohibited by federal, state, or tribal laws or regulations. NIH will also grant exceptions where the federal, state, or tribal prohibition on the use of an sIRB is established by policy. NIH will consider granting an exception if a request is made and a compelling justification provided for why an exception is needed
The text of the publication may be accessed here. The actual policy begins on page 17 of the publication.
On June 1, FDA issued two new guidance documents: one addressing charging for investigational drug and the other discussing FDA’s categorization of investigational devices for CMS reimbursement.
The first guidance is a procedural guidance, “Charging for Investigational Drugs Under an IND“. Using a question and answer format, this guidance answers the questions most frequently asked FDA on obtaining FDA authorization to charge for investigational drug. Under 21 CFR 312.8 Sponsor of an IND must obtain FDA’s authorization in order to charge for an investigational drug for use under the IND. Sponsors do not need to seek FDA authorization to charge for an approved drug used as part of the clinical trial evaluation (e.g., in a clinical trial of a new use of the approved drug, for use of the approved drug as an active control) so long as the drug is obtained from an another, unaffiliated entity.
The second guidance is a draft guidance on “FDA Categorization of Investigational Device Exemption (IDE) Devices to Assist the Centers for Medicare and Medicaid Services (CMS) with Coverage Decisions” (the “Coverage Decision” guidance) modifies the FDA’s current policy on categorizing investigational device exemption (IDE) devices. The FDAs categorization assists the Centers for Medicare & Medicaid Services (CMS) in determining whether or not an IDE device should be covered (reimbursed) by CMS.
The Coverage Guidance sets out the criteria the FDA intends to use to assign a device to a CMS Category A or B. The Coverage Guidance provides examples and includes a flowchart of the FDA’s decision making process. Generally, Category A devices are true “experimental” devices, those for which the initial questions of safety and effectiveness have not been resolved and the FDA is unsure whether the device type can be safe and effective. Category B devices will have existing evidence of safety and effectiveness for the device and/or the intended indication and use either through an existing authorization or clearance for the device or a similar device or there is sufficient non-clinical or clinical data on the device or a sufficiently similar device.
In this June 2016 podcast, Drs. Jacob Doll and Schuyler Jones discuss treatment options related to a randomized trial focused on stent versus surgical options for asymptomatic carotid stenosis patients (ACT-1). Register at the DCRI Learning Center to listen to the free podcast (11:15)
||Jacob Doll, MD
Interventional Cardiology Fellow
Duke University School of Medicine
Schuyler Jones, MD
Assistant Professor of Medicine
Duke University School of Medicine
On May 17, 2016, FDA published a draft guidance on “Use of Electronic Health Record Data in Clinical Investigations.” This short (9 page) guidance provides recommendations on:
- Deciding whether and how to use EHRs as a source of data in clinical investigations
- Ensuring the quality and the integrity of EHR data that are collected and used as electronic source data in clinical investigations
- Ensuring that the use of EHR data collected and used as electronic source data in clinical investigations meets FDA’s inspection, recordkeeping, and record retention requirements
The recommendations outlined in the guidance apply to the use of EHR data in prospective clinical investigations of human drugs and biological products, medical devices, and combination products. This includes foreign clinical studies not conducted under an IND or IDE if data from the studies will be submitted to the FDA.
Among the best practices in the guidance:
- FDA considers the fundamental elements of data quality to be ALCOA. When EHRs are used as a source of data in clinical investigations, sponsors should ensure that the EHRs they use and the processes and policies for their use provide electronic source data that are attributable, legible, contemporaneous, original, and accurate (ALCOA).
- In general, the EHR is identified as the originator of the data elements that are obtained for a clinical investigation in the course of routine clinical care. If data elements are obtained solely for research and entered directly into an EHR by study personnel (e.g., by using a dedicated research module within the EHR) then the person entering the study specific data is the originator.
- FDA will assess compliance with 21 CFR Part 11 on data derived from the EHR at the point where the data enters the sponsor’s electronic system supporting the investigation. The originator of the data elements (i.e., the EHR or study personnel entering or modifying the clinical study data) should be identified along with an electronic date and time stamp in the sponsor’s electronic system. The sponsor should ensure that the appropriate authority controls are in place to limit system access for entering and modifying data to the research component of the EHR to study personnel only.
- FDA urges the use of EHRs that are interoperable with electronic systems supporting clinical investigations. Interoperability means the ability of two or more systems to exchange information and to use the information that has been exchanged. Challenges to interoperability are being addressed by the adoption of data standards as well as through standardization requirements as part of the ONC Health Information Technology (Health IT) Certification Program. Use of such certified EHR technology is encouraged and, if used, gives FDA confidence during inspections that the EHR data is reliable and that the technical and software components of privacy and security protection requirements have been met.
- Non-certified systems must have adequate controls in place to ensure that the confidentiality, integrity, and reliability of data are preserved. To ensure the confidentiality, integrity, and reliability of data, sponsors should consider whether the system has the following internal security safeguards:
- Access to electronic systems is limited to authorized users
- Authors of records are identifiable
- Audit trails are available to track changes to data
- Records are available and retained for FDA inspection for as long as the records are required by applicable regulations
- Sponsors should include (e.g., in the protocol or the data management plan) information about the intended use of the EHR during a clinical investigation and a description or diagram of the electronic data flow between the EHR and the sponsor’s electronic system supporting the clinical investigation. This should include a description of how the relevant EHR data are extracted and subsequently imported into the sponsor’s electronic system. Sponsors should check the extracted data for consistency and completeness with the source data obtained from the EHR, and make corrections when errors are found to properly align the source data with the extracted data.
- In addition to the usual information provided in an informed consent (e.g., who will access the information, the security measures taken to protect confidentiality) when EHRs are being used, sponsors should consider whether there are any reasonably foreseeable risks with the use of EHRs, such as those involving an increased risk of data breaches, that must be described to the subject in the informed consent.
When the EHR is identified as the source, all relevant data within the EHR pertaining to the clinical investigation must be made available to FDA for review upon request. During an inspection, FDA may also request other paper or electronic records to support data in the eCRF (e.g., case histories, other data pertaining to the clinical investigation).
Learn more about a new collaboration between DCRI and SAS that will allow researchers to access data from the DCRI’s Duke Databank for Cardiovascular Disease — the world’s oldest cardiovascular data set.
Researchers can apply for access to the data sets at soar.dcri.org.
Listen to Dr. Janet Woodcock, Director of the Center for Drug Evaluation and Research, define translational science and how it can positively impact drug development and review.