Introduction

During seeding trials, a direct market-research tactic, a company offers their target audience free samples of their new product in exchange for direct feedback on potential uses and advertising for the product. Companies may also gain loyal customers and “opinion-leaders” from this target audience, a result of the audience being the first to use the product.

While this kind of marketing is popular with consumer-products companies, pharmaceutical companies have also created seeding trials of their own, where they ask doctors to use a new drug according to a trial procedure, with the expectation of recruiting these doctors as early loyal users, and possibly advocates for the drug.

Background

One famous example of a successful seeding trial was conducted in the 1970s with Post-it Notes, which did not do well in research tests as “sticky bookmarks.” 3M designed a seeding trial that sent secretaries and other office professionals Post-it Notes, and asked them to come up with uses. Their targets came up with many uses, and started telling others about the product, until Post-it Notes became the ubiquitous office supply many rely on today.

Pharmaceutical companies began the practice of seeding trials in the 1990s, when the companies figured out that conducting clinical trials privately, instead of in the academic world, is quicker and more profitable.

 Issue

Are seeding trials an ethical practice for pharmaceutical companies?

Rule

Seeding trials would be an ethical practice if they were conducted with respect for the patients in mind and with the main intent to study the safety and effectiveness of a drug or a formulation of a drug.

Analysis

While the purpose of a clinical trial is to test the safety and effectiveness of a new drug, or a new formulation or use of a drug that has already been approved, seeding trials occur as Phase IV trials after the drug’s approval, with the purpose of “changing the prescribing habits” of many doctors. Sponsoring companies do not disclose the marketing side of information about the trial; instead, they only release the protocols that will allow them to run the trial. Since the trial’s
Investigational Review Boards (IRBs) only review those published protocols, they are more likely to approve the trial. Also, some IRBs may be chosen and paid by the sponsor simply because the sponsor knows that specific group will approve the trial documents.

Merck’s 1999 ADVANTAGE trial for Vioxx and Parke-Davis’s (now a subsidiary of Pfizer) 1995 STEPS trial for Neurontin are two examples of the harm caused by performing seeding trials.

While conducting the ADVANTAGE trial to assess the gastrointestinal effects of the nonsteroidal anti-inflammatory Vioxx, Merck did not disclose the marketing aspect of the trial to the IRB, investigators, or the patients, even though the marketing department had not only devised the trial but also handled the scientific data “collection, analysis, and dissemination.” The marketing department designed the trial objectives and protocols as well. Internal Merck documents revealed that the purpose of ADVANTAGE was to “entice” more doctors to prescribe the drug. Three patients died during the trial, and 5 suffered heart attacks.

STEPS was an uncontrolled and unblinded study of the safety, efficacy, and tolerability of Neurontin on patients who suffer from partial seizures, with such specific inclusion criteria that generalizing a patient population became impossible. Although this design was questioned, the study continued. Investigators with limited experience were hired and did not receive adequate training. Patients were not informed of the marketing aspect of the trial, the poor design, the inexperienced investigators involved, or of the meal-incentive program for doctors who recruited many patients. Eleven of the 2759 patients in the study died, and 73 suffered serious adverse events.

Not only do these kinds of trials violate the Common Rule for protection of human research subjects, they also violate the trust of the patients, who are seeking relief or a cure, and of the doctors who participate because they are sincerely seeking treatments for their patient, not monetary benefit.

Conclusion

Seeding trials are an unethical, dangerous way to market a product. The IRB needs to become a better-equipped committee that can identify seeding trial practices from honest clinical trials, and the FDA needs to demand more transparency from companies sponsoring clinical trials, to better protect public health and the integrity of clinical research.

For more information on this issue, contact the Kulkarni Law Firm.