Pharma Trix - Seeding Trials

Internal documents made public as part of Vioxx-related litigation show that Merck's marketing department conceived the ADVANTAGE clinical trials as a way to introduce the drug to primary care physicians and turn them into advocates for the product, reported Kevin P. Hill, M.D., M.H.S., of McLean Hospital, and colleagues in the August 19 issue of Annals of Internal Medicine. The researchers said it was the first clearly documented example of a "seeding trial," where marketing a drug to physicians is the main goal, rather than responding to regulatory requirements or answering a scientific question.

They said the practice "threatens the integrity of the relationship of industry, academia, patients, and society" insofar as it disguises the true purpose of clinical trials, thereby undermining the principle of informed consent.

Such trials have long been rumored to be common practice, but documentary evidence had been lacking, Dr. Hill and colleagues said.

Recently, an editorial in the Journal of the American Medical Association suggested that the ENHANCE study of the ezetimibe-simvastatin combination product (Vytorin) was really a seeding trial. However, the authors cited only circumstantial evidence for the allegation.

Jonathan Edelman, M.D., executive director of Merck Research Labs' Global Center for Scientific Affairs, denied that the ADVANTAGE trial had originated with the company's marketing division.

"ADVANTAGE was scientifically driven by [Merck's] clinical research division," he said, which conceived the study and worked with the investigators.

Dr. Edelman said the Annals of Internal Medicine authors "wrongly characterized" the study on the basis of a misreading of the Merck memos and e-mails and a misunderstanding of the company's structure.

The ADVANTAGE study -- published in Annals of Internal Medicine in 2003 -- recruited some 600 primary care physicians as investigators, with each treating about nine patients on average. The trial was conducted just before rofecoxib's FDA approval in 1999, with arthritis patients randomized to rofecoxib or naproxen.

"The purpose of ADVANTAGE was neither to seek a new indication nor to perform post-marketing surveillance," Dr. Hill and colleagues said, noting that the drug's efficacy and tolerability were already addressed at least as thoroughly in other trials.

The researchers found internal Merck memos and presentations in which executives described the ADVANTAGE study's purpose as almost entirely about marketing the drug.

For example, in a memo nominating the trial for an internal marketing award, Merck executives wrote, "The objectives were to provide product trial among a key physician group to accelerate uptake of Vioxx as the second entrant in a highly competitive new class and gather data important to this customer group."

The memo noted that primary care physicians write 60% of prescriptions for arthritis drugs.

"The ADVANTAGE trial utilized this important group of prescribers as investigators. In addition to gaining experience with Vioxx, many of these physicians gained a highly coveted introduction to clinical research."

It also revealed that Merck sales personnel identified physicians to be recruited for the trial and helped monitor the trial's progress.

Source - MedPageToday