A failure of vigilance

Huh? Milder? "Milder" deaths? Really? This statement from the manufacturer's representative, if accurately reported, shows a clear violation of ethical behavior. Reporting to the FDA is mandatory, and had it not been done, legal sanctions would occur. No one is doubting that Amylin and Lilly appropriately reported these cases to the FDA. But failing to report them to an anxious public? Parsing the information so as to hide 4 fatal cases? Sorry, I'm not happy about this.

Nor was the financial community happy. Both Amylin and Lilly took a hit on their stock prices today. As one analyst put it, "We believe more information about these patients with severe pancreatitis could help investors put them in the right perspective. Non-disclosure only leaves more room for speculation." Left unspoken and still to be evaluated is the effect on the confidence of patients and physicians, which also surely took a hit.

What was the failure? It was a failure of pharmacovigilance. Pharmacovigilance is a mandatory activity that every drug company routinely does; it's called "drug safety" by some companies. Entire departments of PV specialists, including physicians, nurses, and other health professionals process incoming reports of "adverse events" and put them into huge computerized safety databases. These PV specialists then forward the reports to the FDA and other Health Authorities in other countries. Then they categorize the reports: how many cases were there of nausea, how many cases of pancreatitis, how many deaths, how many of anything that's reported. So Amylin and Lilly knew (or should have known) precisely how many cases of pancreatitis had been reported.

And one of the first responsibilities of PV physicians is notifying the FDA and their company's management when a "signal" occurs. Fatal cases of an event that is in the label, but not labeled as causing death (such as pancreatitis in the present Byetta label) is one example of a signal. Was the signal missed? Or was the public and perhaps the FDA misled?

Ethics and integrity means that the company should promptly disclose to the FDA that a signal has been spotted. But I believe it's in the best interest of the manufacturer to come clean immediately with full disclosure of what is in their safety databases. Otherwise, as the information slowly leaks out (as it did in this case), one must wonder what else might be in the database. For example, how frequent have abnormalities of the lab tests for pancreatitis (the enzymes amylase and lipase) been reported which were not labeled as pancreatitis by the reporting physicians? Have there been other deaths of patients on Byetta with abnormalities of these enzymes, where the reporting physicians didn't mention "pancreatitis"?

What next? I'd expect the following might occur.

1) Amylin/Lilly might prepare a "Dear Doctor" letter, addressed to health care professionals, outlining what's known to date. These letters take a few days or weeks to prepare, as they need to be reviewed by the FDA and the manufacturer's legal and marketing departments.