A seeding trial or marketing trial is a form of marketing, conducted in the name of research, designed to target product sampling towards selected consumers. In medicine, seeding trials are clinical trials or research studies in which the primary objective is to introduce the concept of a particular medical intervention—such as a pharmaceutical drug or medical device—to physicians, rather than to test a scientific hypothesis.1 In software development, beta-testing may also be referred to as conducting seeding trials.2
To create loyalty and advocacy towards a brand, seeding trials take advantage of opinion leadership to enhance sales, capitalizing on the Hawthorne Effect.2 In a seeding trial, the brand provides potential opinion leaders with the product for free, aiming to gain valuable pre-market feedback and also to build support among the testers, creating influential word-of-mouth advocates for the product. By involving the opinion leaders as testers, effectively inviting them to be an extension of the marketing department, companies can create "a powerful sense of ownership among the clients, customers or consumers that count" by offering engaging the testers in a research dialogue.2 Seeding trials in medicine are not illegal but are considered unethical because they "deceive investigators, clinicians, and patients, subverting the scientific process".3
An early example of a seeding trial was during the development of Post-it notes, produced by 3M. In 1977, secretaries to senior management staff throughout the United States were sent packs of Post-its and invited to suggest possible uses for them. They soon found them to be extremely useful and became "brand champions" for the product, an early example of viral marketing.4
Seeding trials to promote a medical intervention were described as "trials of approved drugs appear to serve little or no scientific purpose" and "thinly veiled attempts to entice doctors to prescribe a new drug being marketed by the company" in a special article in the New England Journal of Medicine. The article, whose authors included U.S. Food and Drug Administration commissioner David Aaron Kessler, also described a number of characteristics common to seeding trials:5
- The trial is of an intervention with many competitors
- Use of a trial design unlikely to achieve its stated scientific aims (e.g., un-blinded, no control group, no placebo)
- Recruitment of physicians as trial investigators because they commonly prescribe similar medical interventions rather than for their scientific merit
- Disproportionately high payments to trial investigators for relatively little work
- Sponsorship is from a company's sales or marketing budget rather than from research and development
- Little requirement for valid data collection
In a seeding trial, doctors and their patients are given free access to a drug and exclusive information and services to use the drug effectively. Additionally, participating physicians are often given financial remuneration and a chance to be a co-author on a resulting scientific publication. By triggering the Hawthorne effect, physicians become "opinion-leading word-of-mouth advocates".2 This practice has been shown to be effective.6
Seeding trials are not illegal, but such practices are considered unethical.178 The obfuscation of true trial objectives (primarily marketing) prevents the proper establishment of informed consent for patient decisions.1 Additionally, trial physicians are not informed of the hidden trial objectives, which may include the physicians themselves being intended study subjects (such as in undisclosed evaluations of prescription practices).1 Seeding trials may also utilize inappropriate promotional rewards, which may exert undue influence or coerce desirable outcomes.1
Documents released during a court case indicate that the Assessment of Differences between Vioxx and Naproxen To Ascertain Gastrointestinal Tolerability and Effectiveness (ADVANTAGE) trial of Vioxx conducted by Merck may have been a seeding trial, with the intention being to introduce the drug to physicians rather than test its efficacy.7910 It appears Merck knew about the potential criticism they would face; an internal email suggested: "It may be a seeding study, but let's not call it that in our internal documents".711 The 2003 study was originally published in the Annals of Internal Medicine12 but was strongly criticized for its deception by the journal's editors in a 2008 editorial, calling for greater responsibility in academia to end the practice of "marketing in the guise of science".13
In another example, the Study of Neurontin: Titrate to Efficacy, Profile of Safety (STEPS) trial14 performed by Parke-Davis to evaluate the anticonvulsant Neurontin may have been a seeding trial.1 Detailed documents were released due to litigation against Parke-Davis and reviewed by several researchers in a 2011 Annals of Internal Medicine article.1 The STEPS trial was presented as a phase IV clinical trial with the stated objective to "study efficacy, safety, tolerability, and quality of life among gabapentin users", however the trial was actually completely uncontrolled and unblinded and the scientific validity of the trial was considered dubious by independent external sources.1 Documents also revealed that the trial recruited 772 physician investigators, many with very limited research experience, provided inadequate training for investigators, and that company sales representatives were "directly involved in collecting and recording individual subject trial data".1
- Krumholz SD, Egilman DS, Ross JS (June 2011). "Study of Neurontin: Titrate to Effect, Profile of Safety (STEPS) Trial: A Narrative Account of a Gabapentin Seeding Trial". Arch. Intern. Med. 171 (12): 1100–7. doi:10.1001/archinternmed.2011.241. PMID 21709111.
- Alexander GC (June 2011). "Seeding Trials and the Subordination of Science: Comment on "Study of Neurontin: Titrate to Effect, Profile of Safety (STEPS) Trial"". Arch. Intern. Med. 171 (12): 1107–8. doi:10.1001/archinternmed.2011.232. PMID 21709112.
- Snopes.com:"Post-It Note Origin". Retrieved 2008-08-21.
- Kessler DA, Rose JL, Temple RJ, Schapiro R, Griffin JP (November 1994). "Therapeutic-class wars--drug promotion in a competitive marketplace". N. Engl. J. Med. 331 (20): 1350–3. doi:10.1056/NEJM199411173312007. PMID 7935706. Retrieved 2008-08-21.
- Andersen M, Kragstrup J, Søndergaard J (June 2006). "How conducting a clinical trial affects physicians' guideline adherence and drug preferences". JAMA 295 (23): 2759–64. doi:10.1001/jama.295.23.2759. PMID 16788131.
- New Scientist: "Merck catches more flak over dangerous drug". Retrieved 2008-08-21.
- Katz KA (March 2008). "Time to nip "seeding trials" in the bud". Arch Dermatol 144 (3): 403–4. doi:10.1001/archderm.144.3.403. PMID 18347299. Retrieved 2008-08-21.
- New York Times: Berenson, Alex (2005-04-24). "Evidence in Vioxx Suits Shows Intervention by Merck Officials". The New York Times. Retrieved 2008-08-21.
- Hill KP, Ross JS, Egilman DS, Krumholz HM (August 2008). "The ADVANTAGE seeding trial: a review of internal documents". Ann. Intern. Med. 149 (4): 251–8. PMID 18711155. Retrieved 2008-08-21.
- Malakoff D (October 2008). "Clinical trials and tribulations. Allegations of waste: the 'seeding' study". Science 322 (5899): 213. doi:10.1126/science.322.5899.213. PMID 18845743.
- Lisse JR, Perlman M, Johansson G, et al. (October 2003). "Gastrointestinal tolerability and effectiveness of rofecoxib versus naproxen in the treatment of osteoarthritis: a randomized, controlled trial". Ann. Intern. Med. 139 (7): 539–46. PMID 14530224.
- Sox HC, Rennie D (August 2008). "Seeding trials: just say "no"". Ann. Intern. Med. 149 (4): 279–80. PMID 18711161. Retrieved 2008-08-21.
- Morrell MJ, McLean MJ, Willmore LJ, Privitera MD, Faught RE, Holmes GL, Magnus L, Bernstein P, Rose-Legatt (June 2000). "Efficacy of gabapentin as adjunctive therapy in a large, multicenter study. The Steps Study Group". Seizure 9 (4): 241–8. doi:10.1053/seiz.2000.0407. PMID 10880282.
- Stephens MD (January 1993). "Marketing aspects of company-sponsored postmarketing surveillance studies". Drug Saf 8 (1): 1–8. doi:10.2165/00002018-199308010-00001. PMID 8471183.