Medical Devices

Clinical Trial Issues Result in Criminal Prosecution - U.S. v. Prigmore, 243 F.3d 1 (1st Cir. 2001)

Related lower court case - Criminal Prosecution for Misrepresentations to the FDA - United States v. Leichter, 160 F.3d 33 (1st Cir. 11-03-1998)

This is a complex case arising from the criminal prosecution of executives of C.R. Bard, Inc., one of the leading manufacturers of catheters used in angioplasty.  Defendants prosecution was based on various claims of defrauding the FDA and selling unapproved medical devices.  The corporation previously entered into a plea agreement that each of the 391 criminal violations it was accused of was committed intentionally. The plea agreement imposed fines of $30,500,000 payable within 30 days as part of the civil settlement; $15,250,000 payable in one year as part of the criminal fine; $15,250,000 payable within two years as the remainder of the criminal fine; and a $78,200 mandatory special assessment. (U.S. v. C.R. Bard, Inc., 848 F.Supp. 287 (D.Mass. 1994).  Prigmore was a Group Executive Vice-President of Bard, with responsibility for the company's United States Catheter and Instrument, Inc. ("USCI") division. Cvinar was President of USCI, and Leichter was USCI's Director of Regulatory Affairs and Quality Assurance.  The instant case is an appeal of defendants' conviction on the underlying fraud and conspiracy and sentence of 18 months imprisonment, and Prigmore's claim that there was insufficient evidence to support his conviction for conspiracy.  A full procedural history is provided in an earlier appeal reported at United States v. Leichter, 160 F.3d 33 (1st Cir. 1998). 

Heart catheters are Class III medical devices, the highest risk class.  Unless they represent technology that was on the market on or before 1976 (see the Buckman case), they cannot be introduced into the marker without going through an intensive premarket approval (PMA) process.  If changes are made in the product that affect its safety and efficacy, these must be approved through the filing of a supplemental PMA application.  Before a new or modified device can be tested on human subjects, the manufacturer must obtain an Investigational Device Exemption (IDE) permit.   In the early 1980s, when angioplasty first became available in this country, USCI controlled 100% of the market for heart catheters. By the late 1980s, however, USCI's market share had declined by about half and the market had become very competitive. When USCI introduced the FDA-approved Probe A in 1987, the device initially sold very well. But the device had a significant limitation. Although USCI marketed Probe A with a label warning that it should not be rotated more than one full turn (360 degrees) in the same direction, physicians performing angioplasties sometimes saw it as necessary to rotate the device beyond its warned-against limitation. When this occurred, the device's balloon had a tendency to wrap itself around the wire, which prevented deflation. This, in turn, blocked blood flow through the artery and complicated efforts to remove the device from the body.  The charges in this and previous cases stemmed from the defendants attempts to maintain market share by bringing a catheter to market that could be rotated more than 360 degrees and still function properly.

"USCI's solution to Probe A's wrapping problem was Probe B, a redesigned version of the same catheter. In Probe A, the balloon attached at the end of the wire, but in Probe B, the balloon attached to a polymer tube threaded over the wire. The result was that Probe B could be rotated more than once in the same direction without the balloon becoming entangled. Unfortunately, however, the new design created different problems.  There was evidence that, in actual use in humans, Probe B's wire broke 25 times more frequently than Probe A's wire. There also was evidence that, when compared to Probe A, these breaks were far more likely to occur when the device was rotated more than once in the same direction. Moreover, the consequences of a Probe B wire break tended to be more serious. In the relatively unlikely event of a Probe A wire break, the catheter's metal tip typically would not detach and could be removed with the wire and balloon. By contrast, when Probe B broke, the broken tip frequently could not be removed with the rest of the catheter. In such a situation, the physician either had to leave the tip in the patient or remove it by invasive surgery. Evidence of these problems poured into USCI in early 1989, but, contrary to the urgings of certain USCI "Crisis Team" members appointed by Cvinar to handle the situation, USCI, and then Bard, declined to order a voluntary recall of Probe B." (from the case)

In the process of bringing Probe B to market, defendants filed a supplementary PMA application which represented that the changed from Probe A had been tested in the lab and did not affect safety and efficacy.  Contrary to these representations, in late October 1988, USCI had begun shipping Probe B catheters for purposes of gathering feedback as to how they performed in humans. There was evidence suggests that this feedback gathering, which USCI called "disaster checking," was for purposes of ascertaining Probe B's rotational capabilities, steerability, and "performance characteristics . . . as compared to the [Probe A]." The government contends that testing for such purposes was safety or effectiveness testing, and thus violated a negative implication to be found in the Class III medical device testing regulations: that an unapproved Class III medical device may not be tested in humans for safety or effectiveness without an IDE.

The key issue in this case cuts to the heart of both device and drug regulation: what is the proper role of labeling for "intended use"?  The FDA regulates formal labeling by manufacturers, and, to a lesser extent, advertising and promotion of drugs and devices.  In many cases, however, drugs and devices are routinely used for unapproved purposes, called "off label" use.  The FDA can not regulate or police off label use because the FDA does not have the authority to regulate the practice of medicine.  The usual issue is whether the manufacturer has crossed the line and is promoting an off label use.  In this case, however, the defendants use the labeling as their excuse for claiming that they had a reasonable belief that they did not need an IND before testing the modified catheter.  Defendants claim that since the label said it should not be turned more than 360 degrees, and the only effects on safety occurred when the modified catheter was turned more than 360 degrees, then the modifications did not effect safety and thus did not need an IDE before testing.  While there was significant evidence that the corporate sales force promoted the modified catheter as being able to be safely turned up to ten revolutions, the defendants claimed this was against company policy and that they had no knowledge of the improper promotion.  This was not very credible because the main competitive problem the modifications addressed was the need to rotate the catheter, but the government did need to rebut this evidence.

The court vacated and remanded, finding that the jury instructions did not sufficiently inform the jury about the standard for resolving disputes about the interpretation of the law.  In particular, the instruction did not mention that if the defendants did reasonably believe that the catheter would never be used so that it was rotated more than 360 degrees, this would be a defense to the government's claim that they intentionally failed to apply for an IDE.  The court opined that there was substantial evidence that defendants did commit the crimes as charged and, based on this, denied defendants motion to reverse and dismiss the charges.  The court also found that there was sufficient evidence to sustain the charges of conspiracy, subject to retrial with the new instructions.