Neurosurgeons at Seattle Grace Hospital are conducting a clinical trial of a new treatment for patients with "rapidly progressive Alzheimer's disease." Some of the patients in the trial are randomly assigned to receive the experimental drug and others are given a placebo. The patients don't know which group they are in, but the doctors find out when they unseal an envelope in the operating room just before inserting the syringe into the patient's brain. Dr. Meredith Grey (Ellen Pompeo), the surgical resident who is coordinating the trial, is anxious to enroll Adele Webber (Loretta Devine), the wife of Seattle Grace's chief of surgery, Dr. Richard Webber (James Pickens Jr.). Adele has been diagnosed with Alzheimer's, and she is becoming more confused. Among other problems, she mistakes Meredith for her dead mother and accuses her of having an affair with Richard. To avoid the risk that Adele will get the placebo, Meredith suggests to Dr. Derek Shepherd (Patrick Dempsey), the neurosurgeon running the trial, that they give her the experimental drug outside the study protocol. But Derek objects on the grounds that it would ruin the trial and "our careers along with it." Despite this warning, Meredith sneaks into the hospital's pharmacy and unseals the envelope for the next patient in the trial. After discovering that Adele is slated to get the placebo, she switches the papers with those in another envelope that instructs doctors to give the drug.
Is rapidly progressive Alzheimer's disease a real condition? Are clinical trials run this way in the real world? Is there a similar type of drug currently under investigation? Would a staff doctor's wife be allowed to participate in a clinical trial at a medical center? Would a doctor who interfered with a trial the way Meredith did get caught, and if so, under what circumstances would her deception come to light? What would be the consequences if her actions were discovered?
The idea that surgeons would be concerned about rapidly progressive Alzheimer's disease is far-fetched to begin with, says Dr. Bruce L. Miller, director of the Memory & Aging Center at UC San Francisco. There are rapidly progressive dementias like prion disorders (including mad cow disease), "but rapid AD just isn't a concept that our field thinks about," he says.
Clinical trials are designed and conducted with great care to ensure valid results that are free of bias, says Joshua Grill, director of the Katherine and Benjamin Kagan Alzheimer's Disease Treatment Development Program at UCLA. According to Grill, proper randomization of patients and making sure they don't know whether they got the drug or the placebo are crucial to preventing bias. Although Meredith acted out of a desire to help a patient, her behavior jeopardized the study by introducing bias and is a case of "scientific misconduct," he says.
Grill says the clinical trial depicted on the show is very similar to an actual multi-center trial that he and other UCLA researchers are participating in as part of the Alzheimer's Disease Cooperative Study. The real study, which relies on decades of research, is testing a virus that has been genetically engineered to stimulate production of a chemical to enhance nerve growth, which could help protect the neurons that are damaged by Alzheimer's. The treatment is delivered directly into the brain in a method similar to the one portrayed in the show.
In both the fictional and the real trial, the small number of surgeons and their teams who do the injections are aware of who gets the treatment and who gets the placebo. That way, if there is a complication during the surgery, the team is prepared to deal with it. Also, the operation for those in the placebo group is less extensive.
But there is a crucial difference between the real world and the TV version. In the real trial, Grill says, the doctors who administer the injections aren't involved in assessing whether the treatment worked. Those assessments are made by doctors who don't know which patients got the drug, so that their clinical judgment isn't influenced — even subconsciously — by the knowledge that a patient did or didn't receive the treatment, he says.
Faculty members and their partners or children would be allowed to participate in clinical trials at their home medical school, Miller adds.
Scientific misconduct can happen — and has happened — in major academic centers, says Dr. Antonio DeSalles, a professor of neurosurgery at UCLA who has studied this phenomenon. When it is discovered, he says, the culprit usually is caught by one of the collaborators who feels betrayed and refuses to participate in the deception. According to DeSalles, when caught, the culprit usually loses his or her job.
Miller points out that in most clinical trials in the U.S., it is not only illegal but "just about impossible" for researchers to tamper with the information that reveals whether a patient will get the drug or the placebo. Unlike the TV rendition, in the real world, control of the study and the drug lies not with the investigators but with the pharmaceutical company or a pharmacist at the hospital, where the drug (or placebo) is identified with a code number. A physician such as Meredith who tampers with a blind study would definitely risk loss of her license or spend time in jail if caught, he says.
Siegel is an associate professor of medicine at New York University Langone Medical Center. His new book is "The Inner Pulse: Unlocking the Secret Code for Sickness and Health."
9 p.m. April 28, ABC
Episode: "It's a Long Way Back"