Medical Device Daily Washington Editor

FDA's governance of clinical investigators has been under some scrutiny for the past couple of years and for the second time in two years, the agency has given notice that it will tighten down on clinical investigators (CIs) with a more aggressive regime for debarment. The agency announced the new rules in the April 13 edition of the Federal Register, which follows an announcement in the summer of 2009 in which FDA indicated it would henceforth move more quickly to strip a CI of his or her clinical trial privileges (Medical Device Daily, Aug. 11, 2009).

Previously, any CI banned from participating in a drug trial could still participate in a device clinical trial and vice versa, but under the new rule, any CI banned from receiving a drug, biologic or device would be barred from all three kinds of trials. The FR notice indicates that the rules will take effect 30 days after the announcement, leaving clinical trial sponsors little time for vetting the roster of CIs participating in their clinical trials. One interesting aspect of the new rule, however, is that the ban would also extend to trials for animal drugs, foods and tobacco products.

The FR notice states that the exhaustive ban on CI participation in clinical trials was “based in part upon recommendations from the Government Accountability Office, presumably a reference to a September 2009 report filed by GAO. FDA states that GAO specifically mentioned that FDA's regulations governing CI disqualification “are included in separate sets of regulations,“ hence limiting the agency's ability to extend a disqualification across product categories. FDA says in the FR notice that it saw “little, if any, evidence that an investigator disqualified from receiving one type of test article . . . later conducted a clinical investigation studying a different type of test article,“ but the agency notes that the comprehensive disqualification “would help to ensure the integrity of clinical trial data“ and “reduce the risk to human subjects.“ This new set of rules, it should be noted, applies to investigators who also are the sponsor of the trial in question.

The FR notice goes into detail on a number of points, including that the effort to harmonize the several regulatory schemes for CI oversight forced a change in the language of several portions of the Code of Federal Regulations, an act of harmonization. One of these would essentially borrow the language from CFR governing device trials for the portions of the CFR addressing these other product categories. For instance, the device regulations that require FDA to notify a CI when the agency is in possession of evidence that the CI has “repeatedly or deliberately“ failed to comply with the relevant requirements – or has “repeatedly or deliberately“ submitted false information to FDA or the sponsor – will be applied in the same fashion to these other portions of CFR.

The proposed rule also mandates FDA will notify the governing institutional review board of any disqualifications. However, the agency indicates it will review any current or approved regulatory applications in which the CI also participated to determine two things. The first is whether that CI's data were corrupted and, in the event the agency determines this is the case, whether the aggregate trial data are still supportive of a safety/efficacy determination. The rule opens the door to a revocation of a marketed product approved under a new drug application, a biologics license application, or a device application if that approval is based on data from a trial in which the CI participated and is found to be problematic.

Regarding CIs in device clinical trials, one difference that seems to have emerged over time is that while FDA is still using warning letters to inform CIs of debarment, it appears that the Center for Devices and Radiological Health is no longer using a letter titled the Notice of Initiation of Disqualification Proceedings and Opportunity to Explain (which bears the ungainly acronym of NIDPOE) to advise the CI of an impending action. Of the five most recent warning letters informing the recipient of the agency's intent to debar, none appear in the NIDPOE database, while the most recent letter in the NIDPOE listing, a November 1, 2010, letter to an Alan Niederman, MD, apparently has no corresponding warning letter.

Despite the apparent decline in the use of NIDPOE letters by CDHR, the April 13 FR notice informs the reader that CDRH, the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research will “furnish the investigator written notice of the matter“ and “an opportunity to explain the matter in writing or, at the option of the investigator, in an informal conference.“ FDA is requesting that comments on the proposed rule be filed by July 12.

NICE completes Doppler assessment

The UK's National Institute for Health and Clinical Excellence announced last year that it was evaluating the use of a device made by Deltex Medical (West Sussex, UK), the CardioQ-ODM Doppler ultrasound unit for surgical monitoring (Medical Device Daily, July 2, 2010), and NICE has decided that the device's use “is supported by the evidence.“

NICE states that data submitted for the CardioQ, which tracks the volume of perioperative blood flow, indicates “a reduction in post-operative complications, use of central venous catheters and in-hospital stay“ with no increase in re-admissions or repeat surgeries “compared with conventional clinical assessment with or without invasive cardiovascular monitoring.“ NICE also states that the cost savings on a per-patient basis “is about £1100 based on a 7.5-day hospital stay,“ noting that the device “should be considered for use in patients undergoing major or high-risk surgery or other surgical patients in whom a clinician would consider using invasive cardiovascular monitoring.“

The agency had issued a draft recommendation late last year for the device (MDD, Oct. 5, 2010), stating at the time that the anticipated per-patient savings would come to £1062, and the final recommendation document reiterates the previously-held belief that while the evidence for the device's use “was particularly convincing for patients undergoing gastrointestinal surgery, benefit was also observed in patients undergoing other types of surgery.“

MHRA issues alert for Philips CT beds

The UK's Medicines and Healthcare Products Regulatory Agency has issues a health alert in connection with several CT scanners made by Philips Healthcare (Guildford, UK). According to the April 12 notice, “nine Philips Healthcare CT scanner beds have the potential to collapse, posing risks to patients undergoing exams.“ The action was prompted by an incident in which “a table holding a patient fell vertically from the upright position“ at a hospital or imaging center the agency declined to identify. MHRA states that the problem “resulted from a failed brake hub.“ Philips is said to be repairing all affected units, a list that includes several of the firm's Brilliance CT and iCT units.

Mark McCarty, 703-268-5690