seeding trial

A seeding trial is a pseudo-clinical trial designed by a pharmaceutical company to promote the use of a product that was recently approved by the U.S. Food and Drug Administration (FDA). "Seeding trials are designed to appear as if they answer a scientific question but primarily fulfill marketing objectives" (Hill et al., 2008). Seeding trials are marketing trials designed to look like clinical trials. Their goal is to give the appearance of doing research while promoting a product. Seeding trials are not designed to discover if a product is safe and effective, but to get doctors to prescribe the product.

In a seeding trial, the marketing department of a pharmaceutical firm recruits physicians to participate in clinical research. The drug company pays the physicians for their participation, designs the study, collects and analyzes the data. The physician has only to prescribe the drug to his or her patients. The typical seeding trial, however, is unlike a proper clinical trial in that it is not blinded, has no controls, subjects don't give informed consent, and placebos are not used.

In such trials, many, many physicians are signed up as investigators, so that each only has to sign up a few patients, and the drug company pays them for each patient and provides all the support necessary for monitoring and paperwork. Meanwhile the reward for physicians participating is the prestige of being an investigator for a clinical trial, coupled with in essence no penalty because the drug company more than reimburses for the time spent, which isn't all that much given that each physician only has to sign up a few patients. In reality, however, the design of the trial is very inefficient. For a real scientific question being tested in a clinical trial, it would be far more efficient to concentrate the patient accrual in a few large academic centers that could find patients much more quickly and already have the infrastructure to do clinical trials. But for seeding trials the scientific question is almost besides the point, an afterthought. The real, unstated purpose of such trials is to expose as many doctors as possible to using the drug and thereby make them comfortable using it. The real purpose of seeding studies is to make these physicians advocates for the new drug. The real purpose of seeding trials is marketing, not science. (Respectful Insolence)

A 1994 article in The New England Journal of Medicine by former FDA commissioner David Kessler et al. states:

Some company-sponsored trials of approved drugs appear to serve little or no scientific purpose. Because they are, in fact, thinly veiled attempts to entice doctors to prescribe a new drug being marketed by the company, they are often referred to as "seeding trials." Features that distinguish such trials from scientifically rigorous studies include the use of a design that does not support the stated research goals, the recruitment of investigators not because they are experts or leading researchers but because they are frequent prescribers of competing products in the same therapeutic class, disproportionately high payments given to "investigators" for their work (although the only work may be to write prescriptions for the drug), sponsorship of the studies by the company's sales and marketing division rather than its research department, minimal requirements for data, and the collection of data that are of little or no value to the company. Typically, these trials involve introducing a new drug in a crowded therapeutic class. The success of such a new product may depend on undoing physicians' comfortable habits of prescribing a competing, more established product (Kessler et al., 1994).

Despite being exposed by the FDA as pseudo-clinical trials, and despite the fact that seeding trials clearly damage public confidence in research by pharmaceutical firms, the practice continues.

Because of being taken to court over the suppressed dangers of Vioxx, documents have become available that, according to Hill et al., show that a study by Merck and Co., Inc., which allegedly investigated the differences between Vioxx and Naproxen, was actually a seeding trial designed to promote Vioxx.* Merck denies the allegations.

The ADVANTAGE clinical trial was designed, conducted, analyzed, interpreted and published by the scientific department of Merck's U.S. Human Health (USHH) organization, Clinical Development (CDP), in conjunction with participating investigators. CDP was part of the Medical and Scientific Affairs department of USHH and was separate from the marketing department within USHH....

ADVANTAGE was a double-blind, randomized, controlled clinical trial with a legitimate scientific purpose designed to answer previously unanswered questions about the use of VIOXX in osteoarthritis in a primary care setting. It was not a seeding study. (Edelmann)

Kevin Hill responded to Merck's denial by noting that documents produced by Merck during one of the lawsuits against Merck that claimed Vioxx caused heart attacks shows the true purpose of the ADVANTAGE study. The documents reveal that Merck’s marketing division designed ADVANTAGE and handled the data collection and analysis. There is also a memo from two top Merck executives nominating the study for an internal marketing award. “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,” the memo states (Silverman).

If created by the marketing division and if one of the purposes of the ADVANTAGE study was to get physicians to prescribe Vioxx, then it was a seeding trial regardless of its design or other purposes. As such, it contributes to the general skepticism of the public regarding the honesty of pharmaceutical companies in conducting clinical research on its products. Because of their deceptiveness, such studies are more damaging to public confidence, when exposed, than those studies that are obviously bogus because they don't even bother to randomize, get informed consent, or provide controls.

further reading

websites

Therapeutic-Class Wars -- Drug Promotion in a Competitive Marketplace by David A. Kessler, Janet L. Rose, Robert J. Temple, Renie Schapiro, and Joseph P. Griffin. The New England Journal of Medicine. November 17, 1994. Volume 331,Number 20, pages1350-1353.

The ADVANTAGE Seeding Trial: A Review of Internal Documents by Kevin P. Hill, MD, MHS; Joseph S. Ross, MD, MHS; David S. Egilman, MD, MPH; and Harlan M. Krumholz, MD, SM. Annals of Internal Medicine. 19 August 2008, Volume 149, Issue 4, pages 251-258.

An Open Letter to the Editors of The Annals of Internal Medicine by Jonathan M. Edelman, M.D. Executive Director, Global Center for Scientific Affairs Merck Research Laboratories

Bad Seed: the ADVANTAGE Trial of Vioxx - Health Care Renewal blog

Seeding trials---no relation to Seed Media Group, LLC - Denialism Blog

When clinical trials are designed by the marketing department - Respectful Insolence blog

Threats to science-based medicine: When clinical trials for new drugs are designed by the marketing division by David Gorski, Science-Based Medicine

A Key Vioxx Study Was Really A ‘Seeding Study’ by Ed Silverman

Seeding trial - Wikipedia

Last updated 21-Oct-2015