Problems put FDA under senator's scrutiny

Food and Drug Administration problems that have attracted the attention of Senator Charles E. Grassley and his investigators:

Antibiotic danger: Investigators continue to seek a face-to-face interview with an FDA special agent who looked into misconduct during the largest of three key trials to measure the safety of the antibiotic Ketek, made by Sanofi Aventis. The doctor leading that clinical trial pleaded guilty to falsifying data, and was sentenced to 57 months. A leaked internal FDA memo dated May 16 this year said Ketek patients have higher rates of acute liver failure and deaths than those using comparable antibiotics .

Dog deaths: After Victoria Hampshire, an FDA veterinary reviewer, told superiors about a spike in side effects and deaths reported for dogs given the heartworm preventive treatment ProHeart 6, she was transferred from her job . Hampshire told Grassley's investigators that the FDA responded to unfounded allegations she had a financial conflict of interest . The Wyeth subsidiary that made the drug pulled it from the market in September 2004 after 5,500 dogs suffered side effects and more than 600 died.

Scientific integrity: A senior FDA staffer last year overruled more than 20 scientists who had spent 15 months reviewing the safety and effectiveness of the Vagus nerve stimulation therapy system, an implant to treat chronic depression . The reviewers said Cyberonics Inc., the device's maker, did not demonstrate a reasonable assurance of its safety and effectiveness for that use.

Vioxx threats: David Graham , who was associate director for science in the FDA's Office of Drug Safety, told Grassley's investigators he was ostracized, intimidated, and ``subjected to veiled threats" when he sought agency permission to present a study that linked Merck & Co.'s painkiller Vioxx to increased risk of heart attack and sudden death . FDA supervisors in August 2004 suggested alerting Merck before publication of the study ``so they can be prepared for extensive media attention that this will likely provoke," according to e-mails released by Grassley's office after the company pulled Vioxx from the market on Sept. 30 , 2004 .

DIEDTRA HENDERSON