Any institution that is based upon science is also dependent upon the integrity of the scientific process, and must guard that integrity jealously. That is certainly one of the missions of Science-Based Medicine. A particular challenge is that medicine is a massively expensive enterprise, and growing in both absolute and relative terms. This means that there is a great deal of money at stake (to be potentially earned and spent) and this fact constantly threatens to distort the process of science that is supposed to underlie medicine.
In particular, wherever there are millions or billions of dollars to be made, the motivation to find clever and subtle ways to distort the scientific process is huge. We find such behavior among any industry that has a medical product or service to sell. A recent example of this behavior was recently published in the Archives of Internal Medicine – Study of Neurontin: Titrate to Effect, Profile of Safety (STEPS) Trial.
Krumholz et al. reviewed the documents resulting from Harden Manufacturing vs Pfizer and Franklin vs Warner-Lambert and concluded:
The STEPS trial was a seeding trial, used to promote gabapentin and increase prescribing among investigators, and marketing was extensively involved in its planning and implementation.
A seeding trial is a pharmaceutical industry term for a clinical trial whose true and stealthy purpose is not to do science but to expose the investigators to a drug. There are often many comparable drugs that can be prescribed for the same indication, and manufacturers therefore want their brand to compete with the others. Also, many drugs are underprescribed and raising awareness among physicians and patients about a disease or condition and the availability of treatments will also serve to increase sales. There are perfectly legitimate ways to accomplish these goals — through honest advertising and medical education, for example.
A seeding trial is a dishonest way to promote a drug. The goal of the trial is to make the physicians who are the investigators in the trial more familiar with the company’s drug. This will demonstrably increase their use of the drug. Further, since “clinical leaders” at academic institutions are often chosen to be investigators, the hope is that they will spread their familiarity and use of the drug to their communities (hence the term “seeding” trial).
The authors of the study make note that marketing was involved in the planning and implementation of the STEPS trial. This is a no-no. Pharmaceutical companies have marketing divisions and research divisions, and they must never “cross the streams.” For example, in optimizing a trial as a seeding trial a company may choose many centers, each of which will recruit a few patients (the STEPS trial had 772 investigators). This maximizes the number of investigators, but is probably not optimal for doing good science.
This type of practice is unethical because it violates the trust of the subjects who enter the trial. As a society we have come to recognize that we have a great responsibility to human subjects of research. People offer themselves up to be experimented on with the understanding — the contract — that the research is legitimate, worthwhile, and every attempt is made to ensure that it is safe and that there is a reasonable probability of benefit. People who entered the STEPS trial did so with the understanding that the study would help improve the practice of medicine, while the real purpose was to promote a product.
The Archives paper gives ample evidence that the STEPS trial was not good science. It was uncontrolled and unblinded, with vague outcome measures. These concerns were even raised prior to implementing the trial. In short — it was bad science, probably because it was designed by marketers.
We can add seeding trials to the list of deceptive practices by industry that distort the science of medicine. This practice was known about prior to the Archives paper — but this is perhaps the best documented instance. I have also written before about companies ghostwriting scientific papers as another example of a deceptive marketing tool. These practices erode the institution of medicine. It seems that eternal vigilance is not only the price of freedom, but scientific integrity as well.