Bioresearch Monitoring Initiatives
A number of initiatives included under the present Strategic Plan for the Center for Devices and Radiological Health (CDRH) are specific to the Division of Bioresearch Monitoring (DBM or BIMO). Some are a continuation of projects or incorporate proposals from the BIMO Reengineering effort. All initiatives are aimed at enhancing DBM's commitment to assure the integrity of data included in submissions to the Center and that clinical trials of medical devices provide the proper human subject protections.
The BIMO Reengineering team developed flow charts to capture the processes related to BIMO's present role in premarket studies. A one-page summary chart is available that includes just the processes, with some additional details for those instances when data reliability concerns arise. A more detailed chart includes the offices and/or personnel with which BIMO personnel interact. It also includes a side-chart of processes specific to data reliability issues.
On-going initiatives include:
Strengthened Communications between ODE and BIMO
To strengthen communications between DBM and ODE, a BIMO Brochure has been developed. It provides a quick reference to the basic interactions possible between BIMO and the ODE divisions and is informative to new ODE reviewers.
In addition, DBM has initiated meetings with ODE to provide a forum to address common interests and/or concerns.
Expansion of Inspectional Strategies
Probability Sampling of Clinical Investigators
In January 2001, BIMO and the Office of Surveillance and Biometrics (OSB) applied for and received additional needs funding to expand on an idea proposed by David W. Feigal, Jr., M.D., M.P.H., the Director of CDRH. His proposal was to develop a probability sampling plan for the Center's clinical investigator inspection program. Probability sampling (PS) is defined as any method of sampling that uses some form of random selection. Any sample analysis done after using this systematic process allows valid statements about the whole population from which a sample is drawn.
Using a systematic sampling method, BIMO would randomly select clinical sites with active IDE studies and issue assignments to the field to inspect these sites. Using information from a specially designed data collection instrument, these inspections will result in a "report card" of the device research community's strengths and weaknesses.
The information obtained from this report card will be used as a management tool to direct scarce resources into areas where there may be a breakdown in human subject protection or data quality systems. BIMO will also use this information to educate the device research community. Armed with this report card, BIMO believes that the device research community will voluntarily institute improvements in their own systems. Subsequently, BIMO will conduct additional probability samplings to measure the impact of any interventions on industry's compliance rate. This should also result in a meaningful measure of BIMO program effectiveness.
Currently, a sampling plan is under development by BIMO and OSB in conjunction with a contractor.
Sponsor Inspections Early in Clinical Studies
This proposal, which is in the early planning stage, would require identification of appropriate studies to audit during the IDE stage. From a listing of on-going IDE studies, BIMO and ODE reviewers would make choices using such parameters as: time elapsed since the initiation of the clinical study, the nature of the device (e.g., break-through products, first of a kind), degree of risk to study subjects, concerns regarding non-clinical study results, and the compliance history of the study sponsor. Well-timed inspections would allow an early assessment of the over-all conduct of the clinical trial, including the adequacy of human subject protections.
The BIMO Package
To facilitate the completion of BIMO inspections, FDA personnel who issue inspection assignments must have available to them all materials relevant to studies that support submissions (the "BIMO package"). It was envisioned that a section of a submission, or possibly even a pre-submission package, would be designated for this use. Despite the use of the word "package," it is not expected that materials included elsewhere in a submission would be duplicated in such a BIMO section, only referenced there. With adequate information provided in the submission or even earlier, it is expected that BIMO inspections would be facilitated. This would provide essential information regarding data integrity and human subject protection to the reviewers in CDRH's Office of Device Evaluation (ODE) earlier in the review process- an asset to both FDA reviewers and medical device sponsors.
A BIMO Reengineering pilot with regard to this issue is still on-going. As of the end of 2001, several companies taking part in the pilot have submitted premarket approval (PMA) applications and at least one has been approved. An initial evaluation of pilot results should be possible during the 2002 fiscal year.
In Vitro Diagnostic (IVD) Guidance
Many studies with unapproved/uncleared IVD devices are exempt from the "Investigational Device Exemptions" (IDE) regulation, Title 21, Code of Federal Regulations (21 CFR) Part 812. Since this is the only regulation that contains FDA's expectations regarding the conduct of studies with investigational medical devices, there has been some confusion in the IVD industry regarding what FDA expects. A sub-team shepherded by the BIMO Reengineering team has drafted a comprehensive guidance entitled "In Vitro Diagnostic (IVD) Device Studies; Draft Guidance for Industry and FDA Staff." The draft is presently undergoing internal review. The guidance includes information regarding IVDs regulated by both CDRH and the Center for Biologics Evaluation and Research (CBER). It is anticipated that this Level 1 guidance document will be available for public comment by late 2002.
Pre-announcement of BIMO Inspections of Sponsors
In recent years, CDRH BIMO inspection assignments associated with marketing submissions usually include an assignment to inspect the study sponsor/monitor and/or their contract research organization (CRO). The present sponsor inspection compliance program (CP7348.10), which is an Agency-wide program, requires that the inspection be unannounced. The CDRH BIMO Reengineering team had proposed that these inspections be pre-announced to help assure the presence of key personnel as well as necessary records and thus expedite the inspection. Subsequently, all FDA Center BIMO staffs agreed with this proposal, and CP 7348.10 will be modified to instruct the field offices responsible for conducting sponsor/monitor/CRO inspections to pre-announce the inspection no less than 5 days in advance. This will apply only to inspections that were not assigned "for cause."
FDA field offices retain the discretion to conduct the inspections unannounced. This change is effective immediately, and CP 7348.10 will be revised during the next regular program review cycle.