One of the major tasks of bioethics since its inception has been to ensure the ethical conduct of scientific experiments involving human subjects. One of the cornerstones of ethical experimentation (indeed of all medical treatment that respects the human dignity of the patient) is the concept of informed consent: the study participant should know up front the purpose, potential benefits, and potential risks of participating in the study.
In the 1990’s, Parke-Davis, the manufacturer of the anti-epileptic medication Neurontin (generic name: gabapentin), conducted a trial called Study of Neurontin: Titrate to Efficacy, Profile of Safety (STEPS). This was a Phase 4 trial (performed after the medication was already on the market) whose professed objective was to study the efficacy, safety, tolerability, and quality of life among gabapentin users as the drug’s dose was increased. Parke-Davis recruited physicians to enroll patients into the trial; in all, 772 physician-investigators enrolled a total of 2759 patients into the trial. The study resulted in two published papers.
It all sounds innocuous enough, no?
Recently, through legal action, all of Parke-Davis’s internal and external documentation relating to STEPS became available for review. In these documents, a different picture of the trial’s objective comes to light. A few quotes from the company’s internal memos:
– “Some indicators of [the study’s] success include 20% increase in new patients’ starts in March and a 3% market share in new prescriptions. . .”
– “STEPS is the best tool we have for Neurontin and we should be using it wherever we can.”
– “. . .at the very least, we should be looking to place as many managed-care patients as feasible in [STEPS] to prevent Lamictal [a competitor’s drug] starts.”
– Multiple strategic planning documents cite the STEPS trial itself, not the trial’s findings, as a key marketing tool for gabapentin.
– Parke-Davis monitored and analyzed the physician-investigators’ prescribing habits, finding increased prescribing of gabapentin among STEPS participants compared to a control group of non-participants.
Apparently, contrary to the trial’s stated objective, the purpose of STEPS was not science, but marketing; the true subjects of the trial were not the patients, but the physicians. The most important measured outcome of the trial was not the safety or efficacy of gabapentin, but whether and how much doctors changed their prescribing behavior as a result of participating in the trial.
Is this an ethical trial? Some might say, sure, there was nondisclosure of the true intent of the trial, but c’mon, it wan’t Tuskegee, right? I mean, nobody was hurt (unless you count the 11 patients who died, the 73 who experienced serious adverse events, and the 997 who experienced less serious adverse effects).
No, this was an unethical trial. There could not be informed consent, as the true purpose of the trial was not revealed to physicians, patients, or IRBs. In addition, using any human being in such a deceptive manner for monetary ends is inconsistent with respect for human dignity.
An article that reviewed STEPS and provided the quotes above appeared in the June 27 Archives of Internal Medicine; the abstract can be accessed here.