A number of e-mails and other internal Merck documents became fair game for analysis and critique when they became available as part of the discovery process of a civil suit involving the cardiovascular safety of Vioxx and this analysis is published in the August 19,2008 issue of the Annals of Internal Medicine . (The Advantage Seeding Trial: A review of Internal Documents, Hill KP et al, Annals Int Med. 2008;149;251-258).
The documents discussed in this article are concerned with a trial called ADVANTAGE which was said to assess the differences between Vioxx and Naproxen regarding side effects and effectiveness in the treatment of osteoarthritis.The trial involved 600 investigators and 2785 patients and was ultimately published in the Annals of Internal Medicine giving the results of a 3 month followup.
The current Annals article(needs subscription) takes the reader into the real life example of the world of a clinical trial that is designed and executed by the marketing ( not the research) division of a pharmaceutical company. This type of trial has been referred to as a "marketing trial" or a "seeding trial". The term " seeding trial" is actually used by involved employees although one company e-mail advised against the use of the term even in in-house writings.Although it has been suspected and alleged that drug companies sponsor these marketing trials this article is said to be the first documentation of at least some of what goes on in the company as the trial is planned and carried out.
Perhaps new to some physicians the seeding trial is nothing new at all in the world of marketing as explained in great detail in this reference which puts the idea in the context of opinion leaders, the Hawthorne effect and the tipping point. (for some reason I could only pull up the cached version.)
If the idea worked for Post-Its-as the above reference explains-why not for prescription drugs?
Psaty and others have decried the use of these low quality ( from a scientific or statistical point of view) trials and I wrote about in 2006 with some fairly unkind words about the physician opinion leaders who participate and make these marketing trials possible.
Doctors Harold Sox and Drummond Rennie wrote the editorial in the August Annals entitled "Seeding trials: Just say "no" " They wrote that the key to a successful seeding trial is deception. I would like to believe that many or most of the physician investigators were deceived as the alternative is that they knew it was wink-wink-nudge-nudge pretense of a trial and the term co-conspirator would apply.
Sox and Rennie said the Annals published the trial because no one told them it was a seed trial.One has to wonder why the editors had to be told. A 1994 NEJM special article made clear the characteristics of such trials and the Advantage trial was published in the Annals in 2003.David Kessler and co-authors in their NEJM article said the following about these marketing 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.
Hopefully with the spotlight of the current Annals article and editorial, editors,review boards and potential physician investigators will be less likely to be deceived and will "say no"and protect the real victims of these trials namely the patients who often in good faith thought they were furthering science and helping other people with the disease under study while in fact they may put themselves at risk for side effects for no reason other than increasing the sales of the medication.