Attention Deficit

WSJ Article Excerpts:

By ANNA WILDE MATHEWS
Staff Reporter of THE WALL STREET JOURNAL
August 24, 2005; Page A1

DOWNEY, Calif. – When Eli Lilly & Co. wanted to get the big California health-maintenance organization Kaiser Permanente to use its new antidepressant, it ran straight into Debbie Kubota.

As the cost of drugs in the U.S. approaches $250 billion a year, pharmaceutical companies are running up against a growing breed of detective trained to see through marketing spin. Working for insurers, state Medicaid programs and nonprofit bodies, these detectives cast a wary eye on published studies in medical journals, once considered an unimpeachable source. They search for subtle aspects of clinical-trial design that might show the drugs are not all they’re cracked up to be.

"You could be duped," says Siri Childs, who oversees pharmacy policy for the Washington state Medicaid program. "We know now that just because it’s published in a medical journal, that doesn’t assure its quality."

The Cochrane Collaboration, a nonprofit that analyzes the quality of studies and collects the ones it considers good into broader analyses, has a volunteer corps of about 7,500 reviewers, mostly doctors and academics. That’s up from about 2,800 five years ago. Another player is the Drug Effectiveness Review Project, an effort by an Oregon nonprofit. It issues reports summarizing all the studies in a particular treatment area and often criticizes individual studies for failings such as inadequate controls and high dropout rates.

Some journals are trying themselves to help readers discover marketing messages slipped in amid the scientific data. Last year BMJ, a British journal, published a piece called "Users’ guide to detecting misleading claims in clinical research reports," which came with a picture of a reader dumping salt on a medical journal. One piece of advice: Beware when the authors break out one subgroup of patients and claim benefits from the treatment that weren’t evident in the whole group.

Dr. Kubota, a 26-year Kaiser veteran who holds a doctor of pharmacy degree from the University of Southern California, is based in the industrial city of Downey, southeast of Los Angeles, across the street from an abandoned movie set. Kaiser tries hard to keep her and her colleagues away from the influence of the companies whose products they evaluate. Before meeting with Dr. Kubota, a representative of a drug company must fill out a form indicating who will be coming, what they plan to discuss and why the information can’t be relayed in written form. No gift pens, mugs or other trinkets are allowed. Dr. Kubota’s business card doesn’t show her direct phone number.

When Dr. Kubota started her current job in 1997, she says she "would just read the abstract," the summary at the beginning of a study. "I guess I was naive," she says. "You kind of assume everything is there for you in the abstract." Today, she quickly homes in on details that aren’t mentioned in the abstract and generates a 6-inch stack of papers studded with Post-it notes for each drug.

When she reviewed Adderall, a stimulant now marketed by Shire Pharmaceuticals Group PLC to treat attention deficit hyperactivity disorder, she noted that one of the major trials included only people who had responded well to Ritalin, another ADHD drug. She thought the move likely improved the results. Dr. Kubota recommended leaving Adderall off Kaiser’s formulary. The physician committees partially overruled her, putting Adderall on the Northern and Southern California formularies but only for patients who failed to respond to another stimulant. Adderall later was added to the preferred list as a first-line treatment after a once-daily formulation went on the market.

A spokesman for Shire, Matt Cabrey, said that the designers of the trial, which was conducted when Adderall belonged to another company, felt that for ethical reasons they should give the drug to people with a "reasonable anticipated reaction." James Swanson, the lead author of the article that described the trial’s results, said the trial was designed to show whether Adderall works faster than Ritalin.